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Biomedical subjects

Y Vulliemoz

Publications and source records attributed to Y Vulliemoz.

At least 37 records · Page 2Linked to original sources
PubMed1984

Developmental changes in adenylate cyclase activity in canine myocardium.

Basal and epinephrine-induced adenylate cyclase activity in homogenates of dog myocardium increased significantly from birth to adulthood, without further change with advancing age. The stimulatory effect of epinephrine (i.e. the net increase over basal activity), however, increased (p less than 0.05) during the first week after birth only and then remained constant. While fluoride-stimulated activity increased, 5'-guanylyl imidodiphosphate [Gpp(NH)p]-stimulated activity declined gradually during development (p less than 0.05). In the presence of Gpp(NH)p and epinephrine at concentrations producing a maximal effect, the enzyme activities in all dogs, except in the 1-day-old, were not significantly different and were comparable to that of fluoride-stimulated activity in adult dogs. The results suggest that age-related alterations in the characteristics of the guanine nucleotide regulatory protein may account, at least in part, for the changes in adenylate cyclase activity occurring during development.

Adenylyl Cyclases↗
PubMed1984

Deuterated halothane--anesthetic potency, anticonvulsant activity, and effect on cerebellar cyclic guanosine 3',5'-monophosphate.

The effect of substituting deuterium for hydrogen in the halothane molecule on anesthetic potency, motor activity, and cerebellar cyclic guanosine 3',5'-monophosphate (cGMP) content was studied in mice. The concentration of halothane required to abolish the righting reflex in 50% of the mice (ED50RR) was chosen as index of anesthetic potency; cerebellar control of motor activity was evaluated by the incidence of isoniazid-induced convulsions. The ED50RR for deuterated (D)-halothane was similar to that of halothane (0.87 +/- 0.04 and 0.88 +/- 0.03 vol%, respectively). Both D-halothane and halothane (0.15-0.90 vol%) protected the mice against isoniazid-induced convulsions and decreased cerebellar cGMP content in a dose-dependent manner. D-halothane and halothane were equipotent on both parameters. Thus deuteration did not alter the anesthetic potency, the anticonvulsant activity, or the effect on cerebellar cGMP content of the anesthetic. Furthermore, the reactivity of the C-H bond is probably not critical for these actions of halothane.

Animals↗
PubMed1983

Effect of enflurane on cerebellar cGMP and on motor activity in the mouse.

The effect of enflurane on the cerebellar content of the intracellular mediator cyclic 3', 5'-guanosine monophosphate (cGMP) and on motor activity was studied in mice. Seizures, as an index of increased motor activity, associated with an increase in cerebellar cGMP content were induced with isoniazide or picrotoxin. Enflurane 0.28-1.68 vol% produced a dose-dependent, reversible decrease in cerebellar cGMP (by about 50% at 0.28 vol%) and delayed or prevented both the increase in cerebellar cGMP and the convulsions induced by isoniazide. Enflurane also protected against picrotoxin-induced convulsions, but not against strychnine-induced convulsions which presumably do not involve cerebellar mechanisms. These results indicate that enflurane affects the cerebellar mechanisms controlling motor activity and it is postulated that this action contributes to the decrease in muscle tone induced by enflurane.

Animals↗
PubMed1982

Senescence-related changes in the responsiveness to ouabain of canine Purkinje fibers.

Clinical studies have suggested that old adults are more susceptible to the toxic effects of digitalis than young adults. To test whether this reflects an age-related change in responsiveness to digitalis of cardiac fibers, standard microelectrode techniques were used to study the effects of ouabain (O) on Purkinje fibers (PF) from 5- and 10-year-old beagles. PF driven at cycle length = 600 msec were superfused with O, 2 x 10(-7) M, containing 3% [3H]O for 25 min. PF-O uptake was the same at both ages. Control maximum diastolic potential, action potential amplitude, upstroke velocity (Vmax) and duration to 50% repolarization (APD50) did not differ significantly between the two age groups. However, the effects of O on action potential characteristics and on delayed after depolarizations in PF from the 10 year old PF were significantly greater than that on the 5 year old PF. Additional experiments were done in which we superfused PF from adult and old animals with O for long periods to determine the time-response relationships for ouabain effects on maximum diastolic potential, action potential amplitude, Vmax and APD50. The rate of change was 2 to 3 times greater in the 10 than the 5 year old PF. After 55 min of O, only 2 of 7 10-year-old PF remained excitable, compared with 6 of 6 5-year-old PF. In conclusion, PF from old dogs show greater responsiveness to the toxic effects of O than those of younger adults, explaining in part the clinical observation of increased digitalis toxicity with age.

Action Potentials↗
PubMed1981

Halothane effect on cGMP and control of motor activity in mouse cerebellum.

The effect of halothane on cerebellar control of motor activity and on cerebellar cyclic 3',5'-guanosine monophosphate (cGMP) content was studied in mice. Isoniazide and picrotoxin were used to increase motor activity and induce seizures associated with an increase in cerebellar cGMP content. Halothane markedly decreased the cerebellar cGMP content (by 60 per cent at 0.61 per cent, the concentration at which 50 per cent of mice lost righting reflex) and prevented the isoniazide-induced increase in cGMP content. Halothane, 0.61 per cent, significantly reduced both isoniazide- and picrotoxin-induced motor activity; the ED50 convulsive dose of isoniazide (137.7 +/- 7.04) and of picrotoxin (1.9 +/- 0.2 mg x kg-1, sc) was about three times higher (402.2 +/- 17.9 and 5.8 +/- 0.6 mg x kg-1, sc, respectively) in mice exposed to halothane. In contrast, halothane did not alter the ED50 convulsive dose of strychnine, which has a different site and mechanism of action, blockade of glycine receptors, a mechanism not involving the cerebellar system. These results indicate that halothane has a significant effect on the cerebellar control of motor activity and that cGMP plays an important role in the alteration of cerebellar function by halothane.

Animals↗
PubMed1981

Halothane effect on beta-adrenergic receptors in canine myocardium.

Halothane depresses the inotropic state of the heart, possibly by decreasing the rate of formation of cyclic 3',5'-adenosine monophosphate (cAMP) through depression of the activity of adenylate cyclase, the cAMP-generating enzyme. As catecholamines regulate the inotropic state and adenylate cyclase activity by binding to myocardial beta-adrenergic receptors, the effect of halothane on binding to these receptors was studied to determine whether this was a site of halothane effect. Beta-adrenergic binding was measured at binding equilibrium in vitro in a canine myocardial membrane preparation in the absence and presence of halothane, 3 to 5 vol%, using as the radioligand 3H-dihydroalprenolol (3H-DHA), a beta-adrenergic antagonist with high affinity and radioactivity. In addition, the effect of halothane on the binding of l-isoproterenol, a beta-adrenergic agonist, was measured by displacement of 3H-DHA. The results indicate that halothane has no effect on either the affinity of canine myocardial beta-adrenergic receptors for 3H-DHA or l-isoproterenol, nor does it alter the number of available receptors at binding equilibrium.

Adenylyl Cyclases↗
PubMed1980

Halothane effect on cAMP generation and hydrolysis in rat brain.

The volatile anesthetic halothane increased the rate of cAMP generation and decreased the rate of cAMP hydrolysis in rat cerebral cortex and cerebellum. The effect of halothane on the enzymes was reflected in a two-fold rise in cAMP content of cerebral cortical tissue exposed to the anesthetic at 3 vol% for 15 and 30 min. The action of halothane on adenylate cyclase is calcium-independent and different from the action of guanine nucleotides, sodium fluoride and specific transmitters. The Vmax of the enzyme is higher in the presence of the anesthetic. It is suggested that halothane, through conformational changes of the enzyme, renders more catalytic sites operative.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1980

Effect of benzothiadiazine derivatives on cyclic nucleotide phosphodiesterase and on the tension of the aortic strip.

Diazoxide and chlorothiazide (0.1--1.5 mM) had a dose-dependent inhibitory effect on the rate of cAMP and cGMP hydrolysis determined in a 500-g supernatant of rat aorta homogenates; both compounds were weaker inhibitors of cAMP and cGMP hydrolysis than theophylline. cAMP and cGMP content of the aorta did not change in the presence of diazoxide or chlorothiazide; diazoxide, however, further increased the isoproterenol-induced rise in cAMP, while chlorothiazide did not. Both benzothiadiazines decreased the maximum tension of the aortic strip induced by serotonin, phenylephrine or potassium. Diazoxide was a stronger and chlorothiazide a weaker inhibitor of the contractile response than theophylline. Comparison of the biochemical and functional effects of diazoxide and chlorothiazide indicates that the inhibitory effect of these compounds on cyclic nucleotide phosphodiesterase does not by itself explain their vasodilating effect.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1980

Effects of halothane on the cyclic 3',5'-adenosine monophosphate enzyme system in human platelets.

A study of the effects of halothane on the cyclic 3',5'-adenosine monophosphate (cAMP) system in human platelets was undertaken since cAMP has been implicated in the regulation of the process of platelet aggregation and this anesthetic has been reported to decrease platelet aggregation and, in other tissues, to increase adenylate cyclase activity. When exposed to halothane 0.5 to 10 vol%, adenylate cyclase activity was increased in the platelet preparation in a dose-dependent manner, reaching a maximum at 5 vol% (93% increase above basal activity). Platelet aggregation was also inhibited by halothane in a dose-dependent manner, with a maximum effect at about 5 vol% halothane (a decrease of 70%). Kinetic analysis of platelet cAMP-phosphodiesterase suggested two forms of activity, neither of which was altered by halothone. The results that the impairment of platelet aggregation observed with halothane may be brought about by the halothane-induced activation of platelet adenylate cyclase, which may result in a higher cAMP level, inhibiting platelet aggregation.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1978

Epinephrine-induced automaticity of canine cardiac Purkinje fibers and its relationship to the adenylate cyclase-adenosine 3',5'-monophosphate system.

We studied the relationship between epinephrine-induced increases in automaticity and in the adenylate cyclase-adenosine 3',5'-monophosphate (cAMP) system in canine cardiac Purkinje fibers. In intact Purkinje fiber bundles superfused with Tyrode's solution, epinephrine induced a concentration-dependent increase in automaticity and in cAMP content. Both of these effects were reduced by propranolol. Decreasing the temperature of the superfusate from 37 degrees to 25 degrees C blocked the epinephrine-induced increase in automaticity, but not the increase in cAMP content. Addition of the metabolic blocking agent, iodoacetate, to the superfusate did not block the effect on Purkinje fiber automaticity, but the cAMP content did not increase. In Purkinje fiber bundle whole homogenates adenylate cyclase was stimulated more by isoproterenol than by epinephrine. Low concentrations of phenylephrine decreased adenylate cyclase activity; higher concentrations induced an increase toward control values. Iodoacetate did not significantly alter cyclase activity and did not affect its response to epinephrine. These students have shown that although intact Purkinje fiber bundles respond to epinephrine with increases in automaticity and cAMP content, these two events can be dissociated under appropriate conditions.

Action Potentials↗
PubMed1977

Cyclic 3',5'-adenosine monophosphate and bronchial tone.

The present studies demonstrate that adenylate cyclase and cyclic 3',5'-adenosine monophosphate (cAMP)-phosphodiesterase activities in dog bronchus are comparable to those found in other smooth muscle preparations. Catecholamines, in the order isoproterenol greater than epinephrine greater than norepinephrine, increase the rate of cAMP formation. This effect can be competitively inhibited by propranolol and potentiated by a cAMP-phosphodiesterase inhibitor. The kinetic study of bronchial cAMP-phosphodiesterase showed two different rates of cAMP hydrolysis, with apparent Km values of 1.4 and 48.0 muM. The high affinity cAMP-phosphodiesterase was inhibited competitively by theophylline and papaverine, the latter being about 20 times more potent than the former. The potency of each compound to inhibit the enzyme and to relax the bronchial strip was comparable. These results, the similar order of potency of the catecholamines to relax the bronchus and to increase the rate of cAMP formation, the competitive inhibition of both effects by propranolol, and the relaxing effect of dibutyryl cAMP on bronchial strip, are compatible with the assumption that the cAMP system is one of the biochemical mechanisms mediating bronchial smooth muscle relaxation.

Adenylyl Cyclases↗
PubMed1977

Adenylate cyclase and phosphodiesterase activity in rabbit ureter.

Adenylate cyclase and phosphodiesterase enzyme activities were demonstrated in rabbit ureter. NaF, 10 mM, caused a 60.9 per cent increase in adenylate cyclase activity. Isoproterenol, 5 X 10-7 to 10-5 M induced a statistically significant dose-dependent increase in adenylate cyclase activity which was suppressed by propranolol, 10-7 M. Theophylline, 5 X 10-5 to 10-2 M, significantly inhibited phosphodiesterase activity. Thus, isoproterenol and theophylline, two agents that can relax ureteral segments previously contracted by a depolarizing concentration of potassium, could presumably increase cyclic AMP levels, isoproterenol by increasing synthesis and theophylline by decreasing degradation.

Adenylyl Cyclases↗
PubMed1975

Ouabain-induced changes in electrophysiologic properties of neonatal, young and adult canine cardiac Purkinje Fibers.

Young patients frequently require higher concentrations of digitalis per kilogram of body weight or per square meter of surface area than adults to induce digitalis effect or toxicity. In order to investigate the electrophysiologic basis for this observation, we used standard microelectrode techniques to study the effects of ouabain on action potential characteristics of cardiac Purkinje fibers of neonatal (1-7 day), 4 to 7 week and adult dogs. Purkinje fibers were stimulated at a 500-msec cycle length. Action potentials were recorded during control Tyrode's perfusion and 23.5 minutes after onset of superfusion with ouabain, 2 X 10(-7) M (10% ouabain-3H). The Purkinje fibers were then assayed for ouabain uptake. Ouabain accelerated repolarization and decreased action potential amplitude, resting membrane potential and maximum upstroke velocity of phase O. Changes were greatest in the adults, least in the neonates. Ouabain increased the slope of phase 4 depolarization in 10 to 12 adults, 7 of 16- 4 to 7-week puppies and 0 of 12 neonates. Hence, ouabain induced lesser changes in the action potentials of Purkinje fibers taken from young animals. These results suggest that Purkinje fiber sensitivity to ouabain effects increases with age.

Action Potentials↗