AJP - Gastrointestinal and Liver Physiology, Vol 248, Issue 5 526-G531, Copyright © 1985 by American Physiological Society
Muscarinic inhibition of canine small intestinal motility in vivo
J. E. Fox, E. E. Daniel, J. Jury and H. Robotham
The quiescent canine gastrointestinal tract responsed to close
intraarterial acetylcholine with an atropine-sensitive, hexamethonium, and
tetrodotoxin-insensitive contraction, thus suggesting acetylcholine
interacts with a muscarinic receptor located on the muscle. When the gut is
actively contracting (spontaneously, in response to field stimulation or to
motilin), acetylcholine caused a contraction followed by prolonged
inhibition of contractions. No such inhibition was apparent after
tetrodotoxin; therefore, the receptor for acetylcholine-induced inhibition
was apparently on nerves. Neither the acetylcholine-induced excitation nor
the inhibition was altered by hexamethonium or reserpine treatment. Both
inhibitory and excitatory responses were greatly reduced by atropine,
suggesting that both receptors were muscarinic in nature. McNeil A343
produced inhibition but no excitation. Tetrodotoxin, hexamethonium,
reserpine, and pirenzepine all increased the concentration of McNeil A343
required for production of 50% inhibition, suggesting it acts via multiple
mechanisms. Furthermore, pirenzepine reduced both the inhibitory and
excitatory response to acetylcholine, suggesting that it is nonselective in
its action on the neural inhibitory or muscular excitatory receptors. We
suggest that the presynaptic muscarinic receptor responsible for inhibitory
effects of acetylcholine is on the postganglionic cholinergic neuron itself
and constitutes an important negative-feedback loop to reduce excessive
cholinergic output. Although such a mechanism has been found in vitro
previously, this is the first report in vivo in canine small intestine.
