AJP - Gastrointestinal and Liver Physiology, Vol 255, Issue 6 779-G786, Copyright © 1988 by American Physiological Society
Characterization of the effects of neurokinins on canine antral muscle
C. B. Koelbel, E. A. Mayer, G. van Deventer, W. J. Snape Jr and A. Patel
Division of Gastroenterology, Harbor-UCLA Medical Center, Torrance 90509.
The excitation of longitudinal antral muscle by substance P (SP) involves
both a myogenic and a cholinergic effect. To examine if these responses are
mediated by different neurokinin receptors, we studied the mechanical
response and the release of [3H]acetylcholine from antral muscle strips in
response to SP, substance P methylester (SPME), neurokinin A (NKA),
neurokinin B (NKB), and several non-mammalian tachykinins. All peptides
studied showed a dose-dependent inotropic and chronotropic effect on
spontaneous phasic contractions. This ionotropic effect in longitudinal
muscle was partially atropine sensitive for SPME, SP, and NKB but not for
NKA, whereas neither atropine nor tetrodotoxin had an effect in circular
muscle. In longitudinal muscle, all three neurokinins were equipotent. In
longitudinal muscle treated with atropine and in circular muscle, the rank
order of potency for the inotropic response was NKA greater than NKB
greater than SP greater than SPME. For the chronotropic response the rank
order was SPME, SP greater than NKA greater than NKB. NKA, NKB, and SP
caused a dose-dependent, tetrodotoxin-sensitive increase in
[3H]acetylcholine release from strips preincubated with [3H]choline. NKA
was significantly more potent to release [3H]acetylcholine than either NKB
or SP. The stimulated release was inhibited by [D-Ala2,D-Met5]methionine
enkephalinamide and the SP antagonist, spantide. These results are
consistent with the hypothesis that NKA is the natural ligand mediating the
myogenic inotropic response in both muscle layers and the cholinergic
response in longitudinal muscle.
