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8433c311-113a-42e7-9d17-848749f7067d
| 3 |
It appears that Ca++ per se is not required for beta agonist or antagonist-receptor interaction in cardiac muscle. The results are discussed in relation to the dependency on extracellular Ca++ for beta agonists to cause a change in the rate of electrical activity after receptor occupancy.
|
861b1b15-9275-4dcd-9754-7221ef07fba9
| 0 |
Effects of isoprenaline and phenylephrine on plasma potassium: role of the liver. A dog liver preparation in situ was used. Intravenous infusion of isoprenaline caused a decrease of plasma potassium levels, which was preceded, in some of the animals infused with higher doses, by a rise in plasma potassium.
|
861b1b15-9275-4dcd-9754-7221ef07fba9
| 1 |
Propranolol abolished both these effects of isoprenaline, whereas phentolamine was devoided of effects. Liver potassium was not affected by isoprenaline infusions. Phenylephrine caused release of potassium from the liver; this effect was blocked by phentolamine, but not by propranolol. Combination of phenylephrine and isoprenaline induced a super-additive hyperkalemia.
|
861b1b15-9275-4dcd-9754-7221ef07fba9
| 2 |
Analysis of these results led to the conclusion that the rise in plasma potassium due to phenylephrine might reflect a direct kalemotropic effect and an indirect hypoxemic effect. Isoprenaline seems to increase the hypoxemia caused by phenylephrine by opening the intrahepatic vascular shunts.
|
ed617b47-7cea-4c3a-afc6-7b9ce2029732
| 0 |
Benzodiazepines and amphetamine on avoidance behaviour in mice. Six benzodiazepine derivatives, given alone or in combination with amphetamine, were tested in mice subjected to five 100-trial avoidance sessions in the shuttle-box. All derivatives, execpt bromazepam, showed some facilitating effects on avoidance responding when given alone.
|
ed617b47-7cea-4c3a-afc6-7b9ce2029732
| 1 |
Facilitation was particularly evident following the administration of chlordiazepoxide (2.5 mg/kg), medazepam (10 mg/kg) and nitrazepam (0.25, 0.5 and 1 mg/kg). Favourable effects were obtained by combining each benzodiazepine compound with amphetamine. The levels of avoidance respinses were usually higher under benzodiazepine-amphetamine combinations than under benzodiazepines alone.
|
a451e0e8-72a4-4771-8692-4b63e16b186e
| 0 |
[Age related effects of furosemide in the rat]. Furosemide (6 mg/kg i.p.) increases the renal excretion of water, osmotic active substances, sodium and chloride in 5 to 33 day old rats more than in adults. The dose-response-relations are the same in rats of all age groups:
|
a451e0e8-72a4-4771-8692-4b63e16b186e
| 1 |
6 mg/kg of furosemide i.p. are very effective, an increase in dose to 30-60 mg/kg i.p. is not followed by a significantly higher efficacy. The increase in the renal excretion of potassium, hydrogen ions, ammonium and hydrogen carbonate by furosemide is also small in young rats.
|
70c3519e-dd4e-4c16-8bdc-11234c5a564c
| 0 |
The effect of sulfhydryl reagents on the heart rate and coronary flow of the isolated perfused guinea-pig heart. The action of a number of compounds able to react with thiols was tested on guinea-pig hearts perfused at constant pressure. The SH reagents used were NaNO2, oxidized glutathione, cystamine, diamide, 1,5-difluoro-2,4-dinitrobenzene, nitroglycerol, sodium nitroferricyanide and HgCl2.
|
70c3519e-dd4e-4c16-8bdc-11234c5a564c
| 1 |
6,6'-Dithiodinicotinic acid, an SH reagent that does not penetrate the cell, produced no effect. All the other SH reagents produced an increase in coronary flow. All except oxidized glutathione and nitroglycerol increased the heart rate. The increase in heart rate and oxygen consumption could be completely blocked by dichloroisoproterenol;
|
70c3519e-dd4e-4c16-8bdc-11234c5a564c
| 2 |
the increase in coronary flow was not affected. Difluorodinitrobenzene, diamide, cystamine and NaNO2 significantly decreased the acid-soluble thiol content of the heart. For these compounds, there was a significant correlation between the decrease in coronary flow and the decrease in thiols. We conclude that in the isolated heart, most SH reagents, if used at the appropriate concentration, will increase the heart rate, probably by relaasing catecholamines.
|
70c3519e-dd4e-4c16-8bdc-11234c5a564c
| 3 |
They will also decrease the coronary resistance, probably by a direct effect on the coronary vessels.
|
e556e940-e1aa-4290-8fc0-8f8672143d4b
| 0 |
Metabolic inhibition and adrenoceptor interconversion. The adrenergic receptor responses of isolated strips of iris dilator muscle from rabbits were studied. An alpha agonist, norepinephrine and a beta agonist, isoprenaline, were used to assess adrenergic sensitivity before and after pretreatment of tissues with metabolic inhibitors at 22, 29 and 37 degrees C.
|
e556e940-e1aa-4290-8fc0-8f8672143d4b
| 1 |
The metabolic inhibitors used were iodoacetic acid and dinitrophenol. Temperature change altered adrenoceptor sensitivity in the same manner before and after metabolic inhibition. Iodoacetic acid (10.4 mug/ml) pretreatment increased both alpha and beta responses. Dinitrophenol (1.8 mug/ml) pretreatment increased alpha and decreased beta responsiveness.
|
e556e940-e1aa-4290-8fc0-8f8672143d4b
| 2 |
The results obtained indicate that some metabolic process altered by dinitrophenol may be involved in this adrenoceptor interconversion seen when temperature is changed. This supports the theory that local environment determines the drug sensitivity (alpha or beta) of a single adrenergic receptor.
|
8271a495-bbf7-4bfa-a4a3-f8483a7c770b
| 0 |
The influence of temperature increase, elevation of extracellular h+-concentration, and of triiodothyronine on the actions of phenylephrine, histamine, and beta-sympathomimetic drugs on rabbit aortic strips. In the isolated preparation from the rabbit thoracic aorta, the affinities of the vasoconstrictor agents phenylephrine and histamine, as well as of the vasodilator beta-sympathomimetic drugs isoprenaline, fenoterol (TH 1165a), terbutaline, and salbutamol under the conditions of temperature increase, triiodothyronine and decrease of extracellular pH were investigated.
|
8271a495-bbf7-4bfa-a4a3-f8483a7c770b
| 1 |
It was observed that (1) a temperature increase from 25 degrees to 42 degrees C significantly indreased the maximal tension evoked by histamine, whereas that induced by the alpha-sympathomimetic drug phenylephrine was not altered significantly; the maximal relaxation caused by beta-sympathomimetic drugs either at 25 degrees or at 42 degrees C did not differ from one another;
|
8271a495-bbf7-4bfa-a4a3-f8483a7c770b
| 2 |
(2) the affinities of histamine, phenylephrine and of the beta-sympathomimetic drugs isoprenaline, fenoterol, terbutaline, and salbutamol each were comparable at either 25 degrees or 42 degrees C; the rank order of efficacy of the beta-sympathomimetic drugs is isoprenaline greater than fenoterol greater than salbutamol greater than terbutaline;
|
8271a495-bbf7-4bfa-a4a3-f8483a7c770b
| 3 |
(3) a decrease of the pH from 7.37 to 7.15 diminished the affinities of histamine and of the beta sympathomimetic drugs whereas that of the alpha-adrenergic drug phenylephrine was not altered. A further decrease of the pH to 6.8 diminished additionally the affinity of histamine and of isoprenaline, and especially that of the other beta-sympathomimetic drugs to such an extent that in the latter case complete dose-response curves could not be determined any more;
|
8271a495-bbf7-4bfa-a4a3-f8483a7c770b
| 4 |
(4) pretreatment of the animals with 0.4 mg/kg of triiodothyronine (T3) for two days, which strongly depressed the tension induced by either histamine or phenylephrine, did not alter the affinity of both drugs; T3 in vitro (10(-6) M) only diminished the affinity of histamine but left that of phenylephrine unaltered;
|
8271a495-bbf7-4bfa-a4a3-f8483a7c770b
| 5 |
pretreatment for two days with 0.2 mg/kg of T3 yielded a significant diminution of the pD2-values for two beta-sympathomimetic drugs investigated, namely isoprenaline and fenoterol; also the administration of T3 in vitro in a final concentration of 10(-6) M resulted in a diminution of the affinity of both beta-sympathomimetic drugs;
|
8271a495-bbf7-4bfa-a4a3-f8483a7c770b
| 6 |
(5) the results obtained show that also on the aorta beta-adrenoceptor stimulants are dependent on the metabolic state while alpha-adrenoceptor stimulants are not.
|
c83b122a-33f9-4c46-b707-8bd176341ed7
| 0 |
Influence of pH on the contractor effect of convulsant barbiturate on frog lung. Pentobarbial, thiopental and the convulsant 5-ethyl-5-(2-cyclohexylideneëthyl) barbituric acid (CHEB) were tested for contractor effect on the isolated lung of the fullfrog at pH 7.0 (7% CO2 and 20 mM HCO3-) and pH 8.4
|
c83b122a-33f9-4c46-b707-8bd176341ed7
| 1 |
(0.3% CO2 and 20mM HCO3-). CHEB was a potent contractor, thiopental a feeble contractor, and pentobarbital lacked contractor effect. The contractor potencies of both CHEB and thiopental were greater at the more acid pH. The potencies of formally charged agonists such as acetylcholine and K+ were not altered by the pH differences employed in these experiments.
|
c83b122a-33f9-4c46-b707-8bd176341ed7
| 2 |
The pKa of CHEB was found to be 8.18 at 15 degrees C and 8.03 at 27 degrees C. Calculation of concentration-effect relationships of ionized and nonionized CHEB showed that only the nonionized CHEB was responsible for the contractor effect.
|
993f80df-77a0-47a4-a7d4-a005b8de8d6c
| 0 |
Action of six commonly used benzodiazepines on isolated guinea-pig ileum preparation. The spasmolytic activity of six commonly used benzodiazepines was investigated on isolated guinea-pig ileum preparation. All six substances proved to be non-competitive antagonists of carbachol and barium chloride, the pD'2 values ranging between 3.23 and 4.37 in the presence of either agonist. The significance of these findings is discussed.
|
fdc7cb9d-f381-48d1-ad7a-bbcf3904167d
| 0 |
Electrical events associated with the action of nicotine at the adrenergic nerve terminal. Nicotine perfused through the coronary circulation of the isolated atropinized cat heart elicits antidromic activity in the cardiac sympathetic nerves. The pattern of discharge varies in a complex fashion with dose. At low concentrations, activity may last up to 10 min, whereas at high doses the antidromic response may last only a few seconds.
|
fdc7cb9d-f381-48d1-ad7a-bbcf3904167d
| 1 |
Sympathetic transmitter is released into the perfusion fluid. There is dissociation between the amount of transmitter that overflows from the heart and the total antidromic activity with increasing dose of nicotine. With smaller doses of nicotine, the magnitude of the antidromic activity probably indicates the level of depolarization of the nerve terminal.
|
fdc7cb9d-f381-48d1-ad7a-bbcf3904167d
| 2 |
Injection of greater doses of nicotine causes still greater transmitter release but not the generation of antidromic impulses, due presumably to persistent depolarization below a critical level. During the nicotine infusion and immediately afterwards, the antidromic response to acetylcholine and the effector responses associated with the adrenergic transmitter release by acetylcholine and sympathetic nerve stimulation were blocked.
|
fdc7cb9d-f381-48d1-ad7a-bbcf3904167d
| 3 |
The rates of recovery of these responses were similar with a half-time of 4 to 5 min. Although the antidromic response to KCl was blocked during the nicotine infusion, it recovered more rapidly. Within 1-1.5 min, the antidromic response to KCl tended to exceed control levels.
|
fdc7cb9d-f381-48d1-ad7a-bbcf3904167d
| 4 |
It is proposed that nicotine causes a prolonged depolarization of the membrane of the adrenergic nerve terminal. The site of action of nicotine, the basis of its prolonged action, and the interrelationship of this depolarization with transmitter release and intracellular uptake are discussed.
|
00163970-b6f2-423d-a989-b2635ec96707
| 0 |
Positive inotropic effect of insulin on rabbit auricle in vitro. Water soluble pig insulin (4 x 10(-8) to 4 x 10(-7) g/ml) produced a marked and long-lasting increase in the contractile force of the rabbit auricle in vitro. Once the maximum effect for a given insulin concentration had been reached, addition of more insulin did not produce any further increase in inotropic effect.
|
00163970-b6f2-423d-a989-b2635ec96707
| 1 |
Insulin was without effect in reserpinized animals. Inhibition of cardiac beta-receptors by propranolol suppressed the positive inotropic effect of insulin. These findings support the hypothesis that insulin releases catecholamines from the myocardium.
|
0fc02420-6e90-4e6e-81c1-689e7d4863e0
| 0 |
Ionic basis for intracellular 14C-nicotine accumulation in slices from different rat brain areas. The effects of ionic alterations on the accumulation, distribution and movements of 14C-nicotine in slices from rat brain striatum, hypothalamus, cortex and cerebellum were studied.
|
0fc02420-6e90-4e6e-81c1-689e7d4863e0
| 1 |
The uptake of 14C-nicotone is not dependent upon Na+ present in the incubation fluid because a K+-substituted (O-Na+) solution increased the 14C-nicotine tissue space, a tris-substituted (O-Na+) solution decreased the 14C-nicotine tissue space and a sucrose-substituted (O-Na+) solution did not change the amount of 14C-nicotine taken up when compared to the 14C-nicotine tissue space obtained in a normal incubation solution. However, all three Na+-free solutions elicited a sustained decrease in 14C-nicotine efflux.
|
0fc02420-6e90-4e6e-81c1-689e7d4863e0
| 2 |
The increase in 14C-nicotine space produced in a K+-substituted (O-Na+) solution was present primarily in the slower component of a two-component washout, whereas the decrease produced in a tris-substituted (O-Na+) solution produced an equal percentage decrease in the size of both components.
|
0fc02420-6e90-4e6e-81c1-689e7d4863e0
| 3 |
Most of the observed effects could be attributed to a linear relationship between the logarithm of the intracellular K+ concentration and the 14C-nicotine tissue space. In conclusion, it appears that there is an intracellular binding site for nicotine and that the degree of binding is dependent upon the concentration of K+.
|
14e59274-dfa0-42c0-9537-8720edfe8192
| 0 |
Mechanism of the antidiuretic effect of beta-adrenergic stimulation in man. Beta-Adrenergic stimulation with isoproterenol hydrochloride in animals causes an antidiuresis similar to antidiuretic hormone. This investigation was undertaken to determine whether isoproterenol inhibits water diuresis in man. Seven young male volunteers were studied during water diuresis in three phases:
|
14e59274-dfa0-42c0-9537-8720edfe8192
| 1 |
(1) water-loading, (2) water-loading plus isoproterenol, and (3) water-loading plus isoproterenol plus propranolol hydrochloride. Antidiuresis occurred 20 minutes following isoproterenol infusion (0.03mug to 0.06mug/kg/min) from a mean of 19.4 to 2.0 ml/min. We found that antidiuresis is due to the hormonal (antidiuretic hormone) and nonhormonal changes (decreased glomerular filtration rate and renal plasma flow).
|
14e59274-dfa0-42c0-9537-8720edfe8192
| 2 |
These in turn are due to the cardiovascular effects of the drug.
|
3a7445f1-3c64-4b2e-854c-6239fcee98f9
| 0 |
Renal acidification in sickle cell trait. Nine sickle cell trait and nine control subjects underwent six-hour ammonium chloride acid loading. Maximal urine osmolality and renal hemodynamics were studied separately. Base line arterial pH, carbon dioxide pressure (Pco2), and [HCO3] were normal and comparable in the two groups.
|
3a7445f1-3c64-4b2e-854c-6239fcee98f9
| 1 |
After ammonium chloride loading, urine pH decreased to 5.3 or less in all, and maximal excretion of ammonium and titratable and net acid was comparable as was urine minus blood Pco2 after bicarbonate loading. The ammonium chloride acidosis caused a small decrease in red blood cell 2,3-diphosphoglycerate levels but no alteration in oxygen pressure at 50% saturation at pH 7.4
|
3a7445f1-3c64-4b2e-854c-6239fcee98f9
| 2 |
, sickling, or adverse effects. Control and sickle cell trait subjects had comparable renal hemodynamics but maximal urine osmolality was lower in sickle-cell trait subjects. Adults with sickle cell trait have diminished renal concentrating ability and normal renal acidification and hemodynamics.
|
724466b6-317c-4d2d-b6bb-0d37e214c63e
| 0 |
Therapeutic implications of gentamicin accumulation in severly diseased kidneys. We evaluated the influence of severe disease in human kidneys (12 patients) on gentamicin sulfate accumulation characteristics in such tissue and compared the results with intrarenal tissue concentration data derived from the study of healthy dogs (54 kidneys) during variation in hydration and urinary pH.
|
724466b6-317c-4d2d-b6bb-0d37e214c63e
| 1 |
Our results indicate that, in the management of pyelonephritis complicating preexisting renal disease, if the minimal inhibitory gentamicin concentration for an infecting organism is greater than the usual therapeutic an nontoxic serum levels of the compound, then it may be appropriate to use alternate antibiotics that demonstrate lesser reduction in tissue drug accumulation in diseased kidneys.
|
f538e57d-4d19-4818-9bb6-8edbd8c8aa93
| 0 |
The influence of pH on the growth and stability of transmissible gastroenteritis virus in vitro. The influence of pH on the growth of transmissible gastroenteritis virus (TGEV) in adult pig thyroid cell culture, and on the stability of the virus was studied. At pH 7.2 and 100 fold higher than those at pH 8.0
|
f538e57d-4d19-4818-9bb6-8edbd8c8aa93
| 1 |
. The adsorption, penetration and uncoating steps of the viral replicative cycle were shown to be unaffected by pH variation. Synthesis of TGEV RNA during the first 12 hours post infection was found to be unaffected by pH variation between the range 6.5-8.0. After 12 hours breakdown of this RNA appeared to occur in cultures held at pH 7.2
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f538e57d-4d19-4818-9bb6-8edbd8c8aa93
| 2 |
and 8.0 but not at pH 6.5. When incubated at 37 degrees C for 24 hours the virus infectivity was found to be least affected by pH 6.5 but when kept at 4 degrees C for the same length of time, the virus infectivity remained constant between pH 5.0
|
f538e57d-4d19-4818-9bb6-8edbd8c8aa93
| 3 |
and pH 8.0.
|
0aa4f385-be59-4767-952a-8bfda5ead61f
| 0 |
The influence of physicochemical factors on the thermal inactivation of murine interferon. The degradation of biological activity of virus-induced murine interferon was determined in linear nonisothermal and multiple isothermal tests. The stabilizing effect of pH during heating on interferon in solution was greatest at low pH, such that pH 2 greater than pH 5 greater than pH 7 greater than or equal to pH 9;
|
0aa4f385-be59-4767-952a-8bfda5ead61f
| 1 |
freeze-dried preparations of interferon were also more heat-stable at acid pH than at neutral pH. Heat stability was a function of the H+-ion concentration rather than the ionic composition of the buffer; interferon solutions containing monovalent cations with different ionic radii had similar heat stability.
|
0aa4f385-be59-4767-952a-8bfda5ead61f
| 2 |
A change in the H+ ion concentration was a critical event during the cooling of heated interferon: a shift in the direction of acidity contributed to stability whereas a shift towards alkalinity led to inactivation. The rate of cooling of heated interferon significantly influenced its residual activity. Rapid cooling and sudden freezing decreased the residual activities of interferons at pH 2 and 9 more than "normal" cooling, an effect not observed at pH 7.
|
0aa4f385-be59-4767-952a-8bfda5ead61f
| 3 |
Interferon heated to 80degree C could not be reactivated at 40degree C or 55degree C. Interferon of higher apparent molecular weight was more heat-stable than that with lower apparent molecular weight. It is postulated that the physicochemical alterations in the aqueous environment significantly affecting the stability of interferon operate by producing changes in the size and/or conformation of interferon molecules.
|
0aa4f385-be59-4767-952a-8bfda5ead61f
| 4 |
A model is proposed that relates thermal inactivation to different possible molecular states of interferon.
|
afc724f7-c0f9-46f0-abcc-72b27c77474c
| 0 |
Isoelectric focusing of herpes simplex virus. Herpes simplex virus was inserted into a preformed stable pH gradient and electrofocused for about one hour. Dextran was used as the density gradient forming agent. Virions banded at pH 4.9+/-0.1 and nucleocapsids at 4.1+/-0.05. About 10-20 per cent of infective virus was recovered.
|
56a29624-8325-4f70-b148-acef7d290ba0
| 0 |
Effect of pH on the growth and cytopathogenicity of avian infectious bronchitis virus in chick kidney cells. The growth of avian infectious bronchitis virus (IBV) in chick kidney cells at different pH values in the range 6.0-9.0 demonstrated that although the virus was released at a much faster rate at the higher pH values the titre tended to drop more quickly.
|
56a29624-8325-4f70-b148-acef7d290ba0
| 1 |
At the acid pH values the virus was released more slowly but reached a maximum titre similar to that at the higher pH values and showed only minimum reduction in infectivity up to 49 hours post inoculation. The stability of virus in tissue culture medium was shown to be directly related to pH 6.0
|
56a29624-8325-4f70-b148-acef7d290ba0
| 2 |
-8.0, being more stable at the acid pH values. The degree of cytopathogenicity induced in chick kidney cells following infection with IBV was directly related to the pH at which the cells were incubated, occurring earlier and more extensively in cells at the higher pH values. Cell macromolecule synthesis in chick kidney cells was inhibited following infection with IBV and was apparently due to cell damage and death.
|
052f30f4-a838-4f98-9582-884d9d3b7435
| 0 |
Eugenol improvement due to aging. A laboratory appraisal. The characteristics of eugenol for dental use appear to improve with age. Exposure to air and light causes certain chemical and physical changes, but the exact nature of the age improvement requires further elucidation.
|
e57780c3-a567-4811-8d0a-df1d243f0e99
| 0 |
Effect of prednisolone and salicyclic acid on ionic fluxes across the human stomach. We compared ionic fluxes across human gastric mucosa after instillation of test solutions of isotonic hydrochloric acid alone or containing salicylic acid, or prednisolone or both. Prednisolone produced no alteration in fluxes of H+ and Na+ ions compared with controls.
|
e57780c3-a567-4811-8d0a-df1d243f0e99
| 1 |
Salicyclic acid induced a significant net loss of H+ ions and gain of Na+ ions indicating alteration of the gastric mucosal barrier. Combined salicyclic acid plus prednisolone produced no increase in permeability of gastric mucosa to H+ and Na+ ions or to salicylic acid itself. Prednisolone was not appreciably absorbed from the stomach while salicylic acid was well absorbed.
|
e57780c3-a567-4811-8d0a-df1d243f0e99
| 2 |
Combination of salicylic acid and prednisolone did not increase absorption of either drug. Neither salicylic acid nor prednisolone solutions alone or combined caused an increase in pepsin output over that due to 160 mM HCl. Salicylic acid resulted in a significant fall in potential difference compared to control while prednisolone produced no change in the one subject studied.
|
e57780c3-a567-4811-8d0a-df1d243f0e99
| 3 |
In acute studies in man prednisolone is not absorbed from the stomach, does not itself affect the gastric mucosal barrier nor pepsin output nor does it enhance the absorption of or effect of salicylic acid on gastric ionic fluxes or pepsin output.
|
007cc457-0a88-47aa-b77f-3cf9378aa5f8
| 0 |
Effects of altering monoamine metabolism on the adrenocortical response to hypoxia. Anesthetized dogs, which had been prepared with lumboadrenal vein cannulae, were intravenously infused with monoamine axidase (alphaETA), tryptophan hydroxylase (pCPA) or tyrosine hydroxylase (alphaMT) inhibitors 30 min prior to exposure to 10% oxygen at ground level.
|
007cc457-0a88-47aa-b77f-3cf9378aa5f8
| 1 |
These studies were designed to ascertain the role of the neurotransmitters, serotonin and norepinephrine, in the adrenocortical response to hypoxia. In normoxic animals, alphaETA decreased basal cortisol secretion and increased systolic pressure, whereas pCPA and alphaMT were essentially without afffect on these parameters. All inhibitors prevented the rise in cortisol secretion usually observed in hypoxic dogs.
|
007cc457-0a88-47aa-b77f-3cf9378aa5f8
| 2 |
Alpha ETA appeared to inhibit the adrenocortical response to hypoxia as a result of its potent pressore activity, while pCPA and alphaMT inhibited cortisol secretion by interfering with the synthesis of serotonin and norepinephrine, respictively. These data suggest that substances which alter the content and/or turnover of brain monoamines abolish the hypoxic rise in cortisol secretion and thus would lower the resistance of the animal to this stressor.
|
32d7d2e1-1972-4adb-b416-0b288f475028
| 0 |
Calcitonin-sensitive adenylate cyclase in rat renal tubular membranes. 1. Renal tubular membranes from rat kidneys were prepared, and adenylate cyclase activity was measured under basal conditions, after stimulation by NaF or salmon calcitonin. Apparent Km value of the enzyme for hormone-linked receptor was close to 1 x 10(-8) M.
|
32d7d2e1-1972-4adb-b416-0b288f475028
| 1 |
2. The system was sensitive to temperature and pH. pH was found to act both on affinity for salmon calcitonin-linked receptor and maximum stimulation, suggesting an effect of pH on hormone-receptor binding and on a subsequent step. 3. KCl was without effect areas whereas CoCl and CaCl2 above 100 muM and MnCl2 above 1 muM inhibited F- -and salmon calcitonin-sensitive adenylate cyclase activities.
|
32d7d2e1-1972-4adb-b416-0b288f475028
| 2 |
The Ca2+ inhibition of the response reflected a fall in maximum stimulation and not a loss of affinity of salmon calcitonin-linked receptor for the enzyme. 4. The measurement of salmon calcitonin-sensitive adenylate cyclase activity as a function of ATP concentration showed that the hormone increases the maximum velocity of the adenylate cyclase.
|
32d7d2e1-1972-4adb-b416-0b288f475028
| 3 |
GTP, ITP and XTP at 200 muM did not modify basal, salmon calcitonin- and parathyroid hormone-sensitive adenylate cyclase activities. 5. Basal, salmon calcitonin- and F- -sensitive adenylate cyclase activities decreased at Mg2+ concentrations below 10 mM. High concentrations of Mg2+ (100 mM) led to an inhibition of the F- -stimulated enzyme.
|
32d7d2e1-1972-4adb-b416-0b288f475028
| 4 |
6. Salmon calcitonin-linked receptor had a greater affinity for adenylate cyclase than human or porcine calcitonin-linked receptors. There was no additive effect of these three calcitonin peptides whereas parathyroid hormone added to salmon calcitonin increased adenylate cyclase activity, thus showing that both hormones bound to different membrane receptors.
|
32d7d2e1-1972-4adb-b416-0b288f475028
| 5 |
Human calcitonin fragments had no effect on adenylate cyclase activity. 7. Salmon calcitonin-stimulated adenylate cyclase activity decreased with the preincubation time. This was due to progressive degradation of the hormone and not to the rate of binding to membrane receptors.
|
814a338f-74cd-4893-837a-3b5a2bb59fad
| 0 |
Stabilization of rat liver tyrosine aminotransferase by tetracycline. Rat liver tyrosine aminotransferase was purified 200-fold and an antiserum raised against it in rabbits. 2. Hepatic tyrosine aminotransferase activity was increased fourfold by tyrosine, twofold by tetracycline, 2.5-fold by cortisone 21-acetate and ninefold by a combination of tyrosine and cortisol administered intraperitoneally to rats.
|
814a338f-74cd-4893-837a-3b5a2bb59fad
| 1 |
3. Radioimmunoassay with 14C-labelled tyrosine aminotransferase, in conjunction with rabbit antiserum against the enzyme, revealed that cortisol stimulates the synthesis of the enzyme de novo, but that tetracycline has no such effect. 4. Incubation of rat liver homogenates with purified tyrosine aminotransferase in vitro leads to a rapid inactivation of the enzyme, which tetracycline partially inhibits.
|
814a338f-74cd-4893-837a-3b5a2bb59fad
| 2 |
5. The inactivation is brought about by intact lysosomes, and the addition of 10mM-cysteine increases the rate of enzyme inactivation, which is further markedly increased by 10mM-Mg2+ and 10mM-ATP. Here again tetracycline partially inhibits the decay rate, leading to the inference that the increase of tyrosine aminotransferase activity in vivo by tetracycline is brought about by the latter inhibiting the lysosomal catheptic action.
|
56fe7bbc-a75c-42be-a7d3-09ee3411af72
| 0 |
Factors regulating amino acid release from extrasplanchnic tissues in the rat. Interactions of alanine and glutamine. 1. Factors regulating the release of alanine and glutamine in vivo were investigated in starved rats by removing the liver from the circulation and monitoring blood metabolite changes for 30 min. 2.
|
56fe7bbc-a75c-42be-a7d3-09ee3411af72
| 1 |
Alanine and glutamine were the predominant amino acids released into the circulation in this preparation. 3. Dichloroacetate, an activator of pyruvate dehydrogenase, inhibited net alanine release: it also interfered with the metabolism of the branched-chain amino acids valine, leucine and isoleucine. 4. L-Cycloserine, an inhibitor of alanine aminotransferase, decreased alanine accumulation by 80% after functional hepatectomy, whereas methionine sulphoximine, an inhibitor of glutamine synthetase, decreased glutamine accumulation by the same amount.
|
56fe7bbc-a75c-42be-a7d3-09ee3411af72
| 2 |
5. It was concluded that: (a) the alanine aminotransferase and the glutamine synthetase pathways respectively were responsible for 80% of the alanine and glutamine released into the circulation by the extrasplanchnic tissues, and extrahepatic proteolysis could account for a maximum of 20%; (b) alanine formation by the peripheral tissues was dependent on availability of pyruvate and not of glutamate;
|
56fe7bbc-a75c-42be-a7d3-09ee3411af72
| 3 |
(c) glutamate availability could influence glutamine formation subject, possibly, to renal control.
|
29aeea44-3e48-482c-a552-064b1b7775fd
| 0 |
Amino acids attached to transfer ribonucleic acid in vivo. 1. tRNA was extracted from rabbit liver by both the phenol and diethyl pyrocarbonate methods under conditions preventing deacylation of the amino acids attached in vivo. 2. After deacylation 12 amino acids were determined by gas-liquid chromatography, by using the flame-ionization and nitrogen-sensitive thermionic detectors.
|
29aeea44-3e48-482c-a552-064b1b7775fd
| 1 |
3. Comparison of the distribution of 12 amino acids attached to tRNA with those contained in total tissue protein and in the free pool showed little correlation. 4. Results for the enzymic charging assay for tRNA in vitro did not correlate satisfactorily with the analysis of amino acids attached to tRNA in vivo.
|
29aeea44-3e48-482c-a552-064b1b7775fd
| 2 |
Marked differences were ntoed in comparison made between our own and other published results.
|
e33ea3de-2e54-4e32-81b4-2bf8103d7a76
| 0 |
Initial rates of pyruvate transport in mitochondria determined by an "inhibitor-stop" technique. An "inhibitor-stop" technique has been developed for measuring initial rates of pyruvate transport into mitochondria. The technique uses alpha-cyano-3-hydroxycinnamate as the inhibitor and separates the mitochondria from the radioactive medium by Millipore filtration. Observed rates depend on availability of hydroxyl and other exchangeable anions within the mitochondrial matrix.
|
c430ab8c-969a-4e82-9a24-ddf200e1eb13
| 0 |
A comparative study between a chondroitinase B and a chondroitinase AC from Flavobacterium heparinum: Isolation of a chondroitinase AC-susceptible dodecasaccharide from chondroitin sulphate B. A chondroitinase that degrades only chondroitin sulphate B was isolated from Flavobacterium heparinum, and separated from a constitutive chondroitinase AC also present in extracts of F.
|
c430ab8c-969a-4e82-9a24-ddf200e1eb13
| 1 |
heparinum. The enzyme acts only on chondroitin sulphate B, producing oligo- and tetra-saccharides, plus an unsaturated 4-sulphated disaccharide (deltaDi-4S). The oligosaccharide fraction (mol. wt. 3000) is susceptible to chondroitinase AC, producing mainly deltaDi-4S. The chondroitinase B is distinguished from chondroitinase AC by several properties, such as the effect of certain metal ions, temperature for optimal activity, and susceptibility to increasing salt concentrations.
|
c430ab8c-969a-4e82-9a24-ddf200e1eb13
| 2 |
The enzyme is induced in F. heparinum by all the chondroitin sulphates, as well as by the disaccharides prepared from the chondroitins. The mechanism of induction of the enzyme and the structure of chondroitin sulphate B are discussed in relation to these results.
|
7f8b606c-d81a-4c0e-9f3c-97b379af6831
| 0 |
Subtilopeptidase A isoenzyme system. Interaction with serum components and its importance for quantitative immunoelectrophoresis. A method was developed which involved electroimmunoassay and crossed immunoelectrophoresis of subtilopeptidase A (EC 3.4.21.14). Initial trials with unfractionated antiserum were not successful and interaction of the enzyme with non-immunoglobulin serum components were shown to be the cause of the failures.
|
7f8b606c-d81a-4c0e-9f3c-97b379af6831
| 1 |
Quantitative immunoelectrophoresis was possible when purified immunoglobulins were used. A pH of 6.5 (lower than the usual pH 8.6) was necessary to obtain a proper baseline definition. Subtilopeptidase A was confirmed as a multiple isoenzyme system. Qualitative inter-batch variations were detected. Di-isopropyl phosphorofluoridate inhibition altered the electrophoretic pattern, but no loss of antigenic determinants was observed.
|
c771190c-b8e9-480f-b2b0-d9a0fce332ed
| 0 |
Fructose 1,6-diphosphate aldolase from rabbit muscle. Effect of pH on the rate of formation and on the equilibrium concentration of the carbanion intermediate. The rate of oxidation of ferricyanide of the aldolase-dihydroxyacetone phosphate complex was measured under different conditions. The following conclusions are drawn. 1.
|
c771190c-b8e9-480f-b2b0-d9a0fce332ed
| 1 |
In the cleavage of fructose diphosphate, catalysed by native aldolase, the steady-state concentration of the enzyme-dihydroxyacetone phosphate carbanion intermediate represents less than 6% of the total enzyme-substrate intermediates. 2. Fructose diphosphate and dihydroxyacetone phosphate compete for the four catalytic sites on aldolase, the binding of fructose diphosphate being about twice as tight.
|
c771190c-b8e9-480f-b2b0-d9a0fce332ed
| 2 |
3. The equilibrium concentration of the carbanion intermediate formed by reaction of carboxypeptidase-treated aldolase with dihydroxyacetone phosphate is independent of pH between 5.0 and 9.0. The rates of fromation of the carbanion intermediate and of the reverse reaction are, however, concomitantly increased by increasing pH between 5.0
|
c771190c-b8e9-480f-b2b0-d9a0fce332ed
| 3 |
and 6.5.
|
d527ea79-f66f-48d0-ad94-eb71dc2e1576
| 0 |
Purification and characterization of a collagenase extracted from rabbit tumours. A collagenase was purified from homogenates of V2 ascites-cell carcinoma growing in rabbit muscle. (NH4)2SO4 precipitation, ion-exchange and gel-filtration chromatography, and affinity chromatography (by using the CB7 CNBr) cleavage fragment of alpha 1(I) collagen linked to agarose) gave a 268000-fold purification and a sevenfold increase in total enzyme units recovered.
|
d527ea79-f66f-48d0-ad94-eb71dc2e1576
| 1 |
The specific activity, defined as mumol of collagen in solution cleaved/h per mg of enzyme at 35 degrees C, WAS 1.74.2. The collagenase had a broad pH optimum from pH7.0 to 9.5, and a mol.wt. of between 33000 and 35000. It was inhibited by dithiothreitol, L-cysteine, D-penicillamine, EDTA and 1,10-phenanthroline, and by both rabbit and human serum.
|
d527ea79-f66f-48d0-ad94-eb71dc2e1576
| 2 |
3. Removal of cations by a chelating resin (Chelex 100) produced as inactive enzyme that could be reactiviated by the addition of Ca2+ ions at concentrations as low as 1muM. Other bivalent cations were not effective. 4. The purified collagenase cleaved peptides alpha2 and alpha1-CB7 (denatured polypeptides of collagen) at 37 degrees C at one site only.
|
d527ea79-f66f-48d0-ad94-eb71dc2e1576
| 3 |
[alpha1 (I)]2alpha2 and [alpha1(III)]3 collagens in solution were cleaved at the same site approximately five times more rapidly than [alpha1 (II)]3. 5. An inhibitor of the enzyme in the tumour extracts, which was dissociable from the enzyme at the (NH4) 2SO4 precipitation step of purification, had a mol.
|
d527ea79-f66f-48d0-ad94-eb71dc2e1576
| 4 |
wt. of between 40000 and 50000 but was distinct from the alpha1 trypsin inhibitor. 6. Studies with zonal density-gradient centrifugation suggested that the enzyme was bound to fibrillar substrate (collagen) extracellularly, but that it was not associated with enzymes originating in cell mitochondria, microsomal preparations or lysosomes.
|
8f0c3ee0-9d9f-4dda-8754-6db5b77c783a
| 0 |
Inhibition of leucocytic lysosomal enzymes by glycosaminoglycans in vitro. 1. A lysosomal fraction was separated by density-gradient centrifugation from a highly purified human polymorphonuclear leucocyte suspension. 2. Some 23 different lysosomal enzymes were assayed for activity in the presence of various concentrations of glycosaminoglycans. 3. The 21 acid hydrolases assayed were strongly inhibited to different degrees by low (0-12 mmol/l) concentrations of glycosaminoglycans in a pH-dependent manner.
|
8f0c3ee0-9d9f-4dda-8754-6db5b77c783a
| 1 |
Thus inhibitions were stronger below pH4.5, with activity returning to control values at about pH5.0. 4. On a molar basis, the inhibitory activity for the several glycosaminoglycans studied was: heparin greater than chondroitin sulphate greater than hyaluronic acid. 5. Once the glycosaminoglycan-acid hydrolase complex was formed, it was partially dissociated by slight elevations in the pH of the incubation medium, by increasing the ionic strength of the incubation medium, or by adding several cationic proteins (e.
|
8f0c3ee0-9d9f-4dda-8754-6db5b77c783a
| 2 |
g. histone, protamine). 6. As leucocytic lysosomes contain large amounts of chondroitin sulphate, and have a strongly acid intragranular pH, we suggest that glycosaminoglycans may modify lysosomal function through the formation of complexes with lysosomal enzymes, by inhibiting the digestive activity of the acid hydrolases when the intralysosomal pH is below their pI.
|
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