Omega-conotoxin GVIA-resistant neurotransmitter release from postganglionic sympathetic nerves in the guinea-pig vas deferens and its modulation by presynaptic receptors.
1 Intracellular recording techniques were used to study neurotransmitter release mechanisms in postganglionic sympathetic nerve terminals in the guinea-pig isolated vas deferens. 2 Recently, a component of action potential-evoked release which is insensitive to high concentrations of the selective N-type calcium channel blocker omega-conotoxin GVIA termed 'residual release' has been described. Under these conditions, release of the neurotransmitter ATP evoked by trains of low frequency stimuli is abolished, but at higher frequencies a substantial component of release is revealed. 3 'Residual release' was studied with trains of 5 or 10 stimuli at stimulation frequencies of 10, 20 and 50 Hz. The alpha2-adrenoceptor agonist clonidine (30-100 nM) inhibited 'residual release', the degree of inhibition being most marked at the beginning of a train. 4 The alpha2-adrenoceptor antagonist yohimbine (1 microM) induced a marked increase in 'residual release' which was dependent on both the frequency of stimulation and the number of stimuli in a train. 5 Prostaglandin E2 (30 nM) and neuropeptide Y (100 nM) caused a rapid inhibition of 'residual release' at all stimulation frequencies examined. 6 4-Aminopyridine (100 microM) induced a powerful potential of 'residual release' and could reverse the inhibition of omega-conotoxin GVIA. 7 'Residual release' was modulated through presynaptic alpha2-adrenoceptors suggesting that (i) residual release of ATP is subject to alpha-autoinhibition through the co-release of noradrenaline, (ii) noradrenaline release can be triggered by calcium channels other than the N-type and (iii) when presynaptic receptors are activated, inhibition of transmitter release can occur by mechanisms other than modulation of calcium-entry through N-type calcium channels in postganglionic sympathetic nerves. Prostaglandin E2 and neuropeptide Y also modulated neurotransmitter release.
Smith
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Department of Physiology and Pharmacology, University of Queensland, St. Lucia, Australia.
Cunnane
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TC
D015761:4-Aminopyridine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009478:Neuropeptide Y / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000502:physiology*; D017779:Sympathetic Fibers, Postganglionic / Q000187:drug effects* / Q000378:metabolism*; D014649:Vas Deferens / Q000294:innervation*; D015016:Yohimbine / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D009478:Neuropeptide Y; D018377:Neurotransmitter Agents; D010455:Peptides; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D020866:omega-Conotoxin GVIA; D015761:4-Aminopyridine; D015232:Dinoprostone; D003000:Clonidine