Interaction of the prejunctional inhibitory action of 5-hydroxytryptamine on noradrenergic transmission with neuronal amine uptake in rabbit isolated ear artery.
The interaction of the prejunctional inhibitory action of 5-hydroxytryptamine (5-HT) on noradrenergic transmission with the neuronal amine uptake mechanism has been studied in rabbit isolated ear artery preparations. Release of norepinephrine in response to stimulation of periarterial sympathetic nerves (30 pulses, 1 Hz) was deduced from the efflux of radioactivity which had been incorporated into the noradrenergic transmitter pool as [3H]norepinephrine. 5-HT (100 nM), applied alone, had no effect on the stimulation-induced efflux of radioactivity. However, in the presence of cocaine (1 microM), 5-HT reduced stimulation-induced efflux. The inhibitory effect of 5-HT, in the presence of cocaine, on stimulation-induced efflux was abolished by the nonselective 5-HT1/5-HT2 receptor antagonist, methiothepin (30 nM), but not by the selective 5-HT2 receptor antagonist, ketanserin (6 nM), or by the alpha adrenoceptor antagonist, phentolamine (30 nM). These findings indicate that the uptake of 5-HT into periarterial sympathetic nerves may limit its prejunctional "5-HT1-like" receptor-mediated inhibitory effect on noradrenergic transmission. In arteries which were incubated with 5-HT (1 microM) and the monoamine oxidase inhibitor, pargyline (10 microM), before loading the transmitter stores with [3H]norepinephrine, methiothepin (30 nM) enhanced stimulation-induced efflux markedly. The enhancing effect of methiothepin was not observed in arteries which were preincubated with cocaine (10 microM) together with 5-HT and pargyline. It is suggested that, following its uptake into periarterial sympathetic nerves, 5-HT may be coreleased with norepinephrine to activate prejunctional 5-HT1-like receptors and thereby mediate an autoinhibitory effect on transmitter release.
Meehan
A G
AG
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Story
D F
DF
D000818:Animals; D001158:Arteries / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology; D004431:Ear, External / Q000098:blood supply; D005260:Female; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D011817:Rabbits; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology*
D011985:Receptors, Serotonin; D012701:Serotonin; D008719:Methiothepin; D007650:Ketanserin; D003042:Cocaine; D009638:Norepinephrine; D010646:Phentolamine