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Interaction of the prejunctional inhibitory action of 5-hydroxytryptamine on noradrenergic transmission with neuronal amine uptake in rabbit isolated ear artery.
J Pharmacol Exp Ther. 1989 Jan; 248(1):342-7.JP

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

2913279

Citation

Meehan, A G., and D F. Story. "Interaction of the Prejunctional Inhibitory Action of 5-hydroxytryptamine On Noradrenergic Transmission With Neuronal Amine Uptake in Rabbit Isolated Ear Artery." The Journal of Pharmacology and Experimental Therapeutics, vol. 248, no. 1, 1989, pp. 342-7.
Meehan AG, Story DF. Interaction of the prejunctional inhibitory action of 5-hydroxytryptamine on noradrenergic transmission with neuronal amine uptake in rabbit isolated ear artery. J Pharmacol Exp Ther. 1989;248(1):342-7.
Meehan, A. G., & Story, D. F. (1989). Interaction of the prejunctional inhibitory action of 5-hydroxytryptamine on noradrenergic transmission with neuronal amine uptake in rabbit isolated ear artery. The Journal of Pharmacology and Experimental Therapeutics, 248(1), 342-7.
Meehan AG, Story DF. Interaction of the Prejunctional Inhibitory Action of 5-hydroxytryptamine On Noradrenergic Transmission With Neuronal Amine Uptake in Rabbit Isolated Ear Artery. J Pharmacol Exp Ther. 1989;248(1):342-7. PubMed PMID: 2913279.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interaction of the prejunctional inhibitory action of 5-hydroxytryptamine on noradrenergic transmission with neuronal amine uptake in rabbit isolated ear artery. AU - Meehan,A G, AU - Story,D F, PY - 1989/1/1/pubmed PY - 1989/1/1/medline PY - 1989/1/1/entrez SP - 342 EP - 7 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 248 IS - 1 N2 - 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/2913279/Interaction_of_the_prejunctional_inhibitory_action_of_5_hydroxytryptamine_on_noradrenergic_transmission_with_neuronal_amine_uptake_in_rabbit_isolated_ear_artery_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=2913279 DB - PRIME DP - Unbound Medicine ER -