AJP - Gastrointestinal and Liver Physiology, Vol 258, Issue 1 122-G128, Copyright © 1990 by American Physiological Society
Neurokinin inhibition of cholinergic myenteric neurons in canine antrum
E. A. Mayer, C. B. Koelbel, W. J. Snape Jr, G. Vandeventer and L. Leduc
Department of Medicine, Harbor-University of California, Los Angeles.
Neurokinins regulate gastrointestinal motility by interacting with
receptors on both muscle layers and on myenteric plexus neurons. To
determine if specific neurokinin (NK) receptor agonists can mediate
inhibitory effects on myenteric neurons, we studied the effect of the NK-1
agonist substance P methylester (SPME) and the putative endogenous NK-2
receptor ligand neurokinin A (NKA) on [3H]acetylcholine [( 3H]ACh) release
induced by electrical field stimulation from muscle strips cut from the
canine gastric antrum. SPME but not NKA caused a dose-dependent inhibition
of stimulated [3H]ACh release in tissues containing the myenteric plexus.
The inhibition was not seen in longitudinal muscle without myenteric
plexus. Pretreatment of tissues with indomethacin or antiserum to
vasoactive intestinal polypeptide (VIP) but not naloxone or adrenergic or
cholingergic blockade abolished the SPME-induced inhibition. Exogenous VIP
stimulated the release of prostaglandin E2 (PGE2) from full thickness
strips, and both VIP and PGE2 inhibited [3H]ACh release induced by
electrical depolarization. These findings suggest that NK-1 receptor
agonists can selectively inhibit stimulated [3H]ACh release and that this
inhibition may involve the release of VIP and PGE2 from neurons within the
myenteric plexus.
