We studied the effects of close intra-arterial injections of substance P on colonic motor activity in the conscious state, during anesthesia, and during acute laparotomy. In the conscious state, with enteric nerves intact, substance P stimulated postsynaptic cholinergic neurons to induce a large amplitude and long duration contraction. This response was blocked by prior close intra-arterial injection of atropine and tetrodotoxin (TTX) but not hexamethonium. Hexamethonium and TTX given alone, close intra-arterially, induced a series of short-duration contractions. Prior close intra-arterial administration of hexamethonium significantly enhanced the colonic motor response to substance P. After blockade of nerve conduction by TTX, substance P induced a series of short-duration contractions with characteristics different from those when the nerves were functioning. Anesthesia alone had little effect on the colonic motor response to substance P, but laparotomy inhibited it significantly. Laparotomy similarly inhibited the contractile response to bethanechol. Gut handling had no further effect on this inhibition. We conclude that in the conscious state substance P acts preferentially on postsynaptic cholinergic neurons to contract colonic circular muscle. When the intrinsic nerves are blocked, substance P may act directly on the smooth muscle to induce circular muscle contractions with characteristics different from those induced when nerves are intact. Substance P also has a weak inhibitory motor effect by its action on presynaptic neurons that synapse on postganglionic intrinsic inhibitory neurons. Anesthetic doses of barbiturates have no major effects on the neuromuscular response to substance P, but laparotomy significantly inhibits the smooth muscle response and selectively blocks some neurons.
Increase in neurokinin-1 receptor-mediated colonic motor response in a rat model of irritable bowel syndrome