Muscarinic inhibition of canine small intestinal motility in vivo

Abstract

The quiescent canine gastrointestinal tract responsed to close intraarterial acetylcholine with an atropine-sensitive, hexamethonium, and tetrodotoxin-insensitive contraction, suggesting acetylcholine interacts with a muscarinic receptor located on the muscle. When the gut was actively contracting (spontaneously, in response to field sitmulation 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. NcNeil A343 [4-(m-chlorophenylcarbamoyloxy)-6-butyryltrimethylammonium chloride] 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. 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. The presynaptic muscarinic receptor responsible for inhibitory effects of acetylcholine is apparently on the postganglionic cholinergic neuron itself and constitutes an important negative-feedback loop to reduce excessive cholinergic output. Although such a mechanism was found in vitro previously, this is seemingly the first report in vivo in canine small intestine.