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Y Oron

Publications and source records attributed to Y Oron.

84 records · Page 5Linked to original sources
PubMed1980

Stable cholinergic-muscarinic and alpha-adrenergic inhibition of rat parotid adenylate cyclase.

(-) Isoproterenol-stimulated adenylate cyclase activity of washed at parotid membrane preparations from gland slices previously treated with the alpha-adrenergic agonist, methoxamine, was inhibited approximately 30%. The action of methoxamine required exogenous Ca2+ and was blocked by the alpha-adrenergic blocking agent, phentolamine. Incubation of gland slices with carbamylcholine resulted in a dose-dependent inhibition (50%) of (-) isoproterenol-stimulated adenylate cyclase activity in washed membranes. The action of carbamylcholine was independent of exogenous Ca2+ and was blocked by preincubation with atropine. Cholinergic inhibition of parotid adenylate cyclase was compared to the cholinergic inhibition of adenylate cyclase in dog heart homogenates. While carbamylcholine caused a limited (20-30%) inhibition of basal and (-) isoproterenol-stimulated activities when added to dog heart homogenates, it failed to produce any effect in parotid homogenates prepared in an identical manner. Cholinergic inhibition of parotid adenylate cyclase activity was stable and persisted in washed particulate fractions while the inhibition in dog heart homogenates was reversible by washing. Cholinergic inhibition of adenylate cyclase was markedly dependent on the presence of GTP and was abolished when Mn2+ was subsituted for Mg2+ in both systems. Guanyl-5'-yl imidodiphosphate had little effect on the inhibition in parotid preparations but abolished the inhibition in heart homogenates. It is concluded that, in contrast to the cholinergic action in dog heart homogenates, the exposure of parotid slices to carbamylcholine results in a stable lesion in the adenylate cyclase activity.

Adenylyl Cyclase Inhibitors↗
PubMed1978

Amylase activity, glycoprotein and electrolyte concentration in rat's submaxillary salivary gland during heat acclimation.

1. Amylase activity, glycoproteins, Na and K concentrations were measured in submaxillary salivary gland of the rat during heat acclimation (34 degrees C). 2. Acclimation resulted in a decrease in glycoprotein concentration and amylase activity, whereas Na and K concentrations and the Na/K ratio increased. 3. It is suggested that heat acclimation results in an increase in glandular activity leading to increased water secretion and depletion of the glycoprotein store. The decrease in amylase activity is probably due to liver atrophy which occurs during prolonged heat exposure.

Acclimatization↗
PubMedDate not supplied

Inositol 1,4,5-trisphosphate mimics muscarinic response in Xenopus oocytes.

The enhanced metabolism of phosphoinositides, which is associated with a wide variety of stimuli and physiological responses, has been studied intensively. Berridge and his collaborators demonstrated that the first measurable reaction following cell membrane receptor activation is a rapid hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), and that the product of this reaction, inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), could cause a release of non-mitochondrial calcium. These findings have been verified in other systems. Although the relationship between the hydrolysis of PtdIns(4,5)P2 and the mobilization of intracellular calcium was clearly demonstrated, the direct link between Ins(1,4,5)P3 production and the physiological response was only implied. We have investigated the possibility that the intracellular release of Ins(1,4,5)P3 mediates the muscarinic-cholinergic response is Xenopus oocytes, and we show here that intracellularly injected Ins(1,4,5)P3 mimics the muscarinic depolarizing chloride current in Xenopus oocytes. This is the first demonstration of a direct link between phosphoinositides metabolism and a neuro-transmitter-induced physiological response.

Animals↗
PubMedDate not supplied

Positive inotropic response to alpha-adrenergic stimulation in an electrically driven rat left atrium: the role of extracellular calcium.

We studied the positive inotropic response induced by alpha-adrenergic receptor stimulation in an electrically driven rat left atrium. alpha-Adrenergic stimulation resulted in a prolonged positive inotropic response that reached its maximum within 5-7 min. The kinetics of the onset of the positive inotropic response were different for pure alpha-adrenergic, pure beta-adrenergic, and mixed adrenergic stimulation. The positive inotropic responses to alpha- and beta-adrenergic agonists were not additive. The relative inotropic response to alpha-adrenergic stimulation decreased when external calcium concentration was increased and disappeared when external calcium concentration was raised to 7.0 mM. The divalent cation ionophore A23187 (1 microM) produced a threefold increase of the contractility of the atrial preparation at 1.0 mM extracellular calcium, and no further alpha-adrenergic response was observed in its presence. Calcium channel antagonists verapamil and nifedipine markedly inhibited the response to alpha-adrenergic stimulation, with little effect on the beta-adrenergic stimulation, at a calcium concentration of 0.5 mM. The inhibitory effect of calcium channel antagonists could be fully reversed by increasing the extracellular calcium concentration. Our data suggest that the alpha-adrenergic contractile response in the rat atrium involves the mobilization of extracellular calcium through verapamil-sensitive calcium channels in a mechanism different from that for the beta-adrenergic response.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

The metabolism of microinjected inositol trisphosphate in Xenopus oocytes.

Microinjection of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) into Xenopus oocytes evokes a complex physiological response composed of a transient and a slow depolarizing chloride current. We investigated the relationship between intracellular levels of Ins(1,4,5)P3 and the kinetics of the physiological response. Microinjected Ins(1,4,5)P3 was slowly degraded following first order kinetics of disappearance (t1/2 = 10 min). The degradation products were inositol bisphosphate (InsP2), inositol monophosphate (InsP) and inositol, as well as inositol tetrakisphosphate (InsP4). The rate of degradation of injected 3[H]-Ins(1,4)P2 was much greater (t1/2 = 3 min), indicating that the conversion of InsP3 to InsP2 may be the rate-limiting step in the degradation process. The slow degradation of 3[H]-Ins(1,4,5)P3 was not a result of its conversion to Ins(1,3,4)P3 since no accumulation of InsP3 was observed within 10 min of microinjection of 3[H]-Ins(1,3,4,5)P4. Activation of protein kinase C (PK-C) with a phorbol ester transiently increased the rate of conversion of 3[H]-Ins(1,4,5)P3 to InsP2. This, however, did not significantly affect the overall kinetics of 3[H]-Ins(1,4,5)P3 disappearance. Our results indicate that the kinetics of Ins(1,4,5)P3 degradation do not correlate well with the termination of both the rapid and the slow components of the physiological response. The termination of the slow component of the response, however, may be related to the decay of Ins(1,4,5)P3-induced 45Ca efflux, which lasted about 10 min.

Animals↗
PubMedDate not supplied

The hemispheric distribution of Torpedo nicotinic receptors expressed in Xenopus oocytes.

The physical and the functional distribution of Torpedo nicotinic-cholinergic receptors expressed in Xenopus oocytes was assayed. Physical hemispheric receptor distribution was tested by binding of 125[I]-bungarotoxin. The density of the expressed nicotinic receptors was equal on both hemispheres (ratio animal/vegetal = 1.1 +/- 0.2). Functional distribution was tested either by whole hemispheric response assay or by monitoring responses from small areas on the two hemispheres. While the first method yielded results that suggested uniform receptor density distribution, the second method indicated two-fold higher responsiveness on the animal hemisphere, when compared with the vegetal hemisphere. Direct comparison on oocytes of the same donors did not reveal significant differences between the two assays. We did see, however, a high variability among the different donors (animal/vegetal activity ratio range 0.5-4.7). Overall, in 35 experiments in 18 donors, the animal/vegetal ratio of hemispheric responsiveness was 1.4. The possible source of this high variability may have been the large excess of bungarotoxin-binding sites over the number of active channels. We have also tested hemispheric responsiveness ratio with different concentrations of acetylcholine. When acetylcholine concentration was below 10 microM, the animal/ vegetal ratio was significantly lower than 1.0. Similar results were obtained with nicotinic receptors expressed after injection of RNA transcribed in vitro from cloned mouse nicotinic receptor subunits. These results imply that hemispheric membrane heterogeneity may affect receptor and/or channel activities to yield polarized channel activity despite nearly homogeneous receptor distribution.

Animals↗