AJP - Gastrointestinal and Liver Physiology, Vol 264, Issue 3 454-G461, Copyright © 1993 by American Physiological Society

ARTICLES

Adenosine and 5-HT inhibit substance P release from nerve endings in myenteric ganglia by distinct mechanisms

R. M. Broad, T. J. McDonald and M. A. Cook
Department of Pharmacology and Toxicology, University of Western Ontario, London, Canada.

Release of substance P-like immunoreactivity (SP-LI) from dissociated enteric ganglia and the receptor-mediated prejunctional inhibition of this release were investigated with the use of a perifusion technique. SP-LI release was evoked by elevated extracellular K+ concentration and was inhibited, in a graded manner, by N6-cyclopentyl adenosine (CPA), an adenosine analogue with selectivity for adenosine A1 receptors. Similar inhibition of SP-LI release was obtained with 5-hydroxytryptamine (5-HT); incrementing concentrations, however, yielded a biphasic concentration-response relationship. The selective adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentyl-xanthine abolished the inhibition due to CPA, whereas the inhibitory action of 5-HT was sensitive to the 5-HT1A-selective antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]-piperazine hydrobromide. Inhibition due to both agonists was insensitive to blockade by tetrodotoxin, suggesting a prejunctional locus for both adenosine and 5-HT1A receptors on the tachykininergic nerve endings. Pretreatment of ganglia with pertussis toxin had no effect on CPA-mediated inhibition of SP-LI release, whereas 5-HT-mediated inhibition was abolished. The findings demonstrate that adenosine and 5-HT receptors on enteric nerve endings are coupled to inhibition of tachykinin release through distinct mechanisms, putatively distinct G proteins.

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