Endogenous adenosine inhibits evoked substance p release from
perifused networks of myenteric ganglia.
Moneta, N. A., T. J. McDonald, and M. A. Cook.
Departments of Pharmacology and Toxicology, Medicine and Robarts
Research, Institute, University of Western Ontario, London, Ontario,
Canada
APStracts 3:0150G, 1996.
Isolated myenteric ganglion networks were prepared from guinea pig
ileum and were used in a perifusion protocol to examine the effects
of interstitial adenosine on evoked release of Substance P-like
immunoreactivity. The release of SP-LI evoked by elevated
extracellular K+ concentration, was increased in the presence of TTX
indicating tonic inhibition of SP-LI release and revealing net
inhibitory interganglionic transmission. Perifusion in the presence
of the adenosine A1 receptor-selective antagonist 1,3-dipropyl-8
-cyclopentylxanthine (DPCPX) enhanced evoked SP-LI release which was
further enhanced in the additional presence of TTX indicating that
adenosine contributes some, but not all, of the overall inhibitory
tone within the networks. In addition to neural release of adenosine
per se, an additional source was investigated. Perifusion in the
presence of [alpha], -methylene-ADP plus 5'-GMP, which inhibits
ectoATPase activity, enhanced SP-LI release indicating that
hydrolysis of released ATP contributes to the total interstitial
nucleoside concentration and thereby to the overall inhibitory tone.
It is concluded that endogenous adenosine, some of which arises from
ATP metabolism, is an important contributor to the overall inhibitory
tone present in myenteric ganglion networks.
Received 5 December 1995; accepted in final form 26 July 1996.
APS Manuscript Number G512-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996