Neural control of the sphincter of Oddi. A physiological role of 5-hydroxytryptamine in the regulation of basal sphincter of Oddi motor activity in the cat.

The effect of 5-hydroxytryptamine (5-HT) on the sphincter of Oddi (SO) was studied in the cat. The SO had two motor responses to 5-HT: the most common was an initial contraction followed by a more prolonged relaxation, and the other was an exclusive relaxation. Tetrodotoxin did not impair the magnitude of the net contraction induced by 5-HT, but it completely blocked the relaxation. Methysergide partially inhibited the SO contraction in response to submaximal doses of 5-HT (5-20 micrograms/kg). Atropine decreased the SO excitatory response to all doses of 5-HT. The combination of atropine and methysergide completely antagonized the 5-HT excitatory effect, which changed the SO biphasic response to an exclusive relaxation. After tetrodotoxin, the effect of 5-HT was almost completely antagonized by methysergide alone. The SO contraction and relaxation caused by 5-HT were almost completely blocked by 5-HT tachyphylaxis. In contrast, a 5-HT depletion with reserpine enhanced the sensitivity of the SO to 5-HT, responding to doses a thousand times smaller than in control animals. Hexamethonium, phentolamine, propranolol, and 5-methoxy-N,N-dimethyltryptamine did not antagonize the 5-HT-induced contraction or relaxation. These findings indicate that 5-HT caused SO contraction by stimulating postganglionic cholinergic neurons and the smooth muscle directly and caused relaxation by stimulating postganglionic, noncholinergic, nonadrenergic inhibitory neurons. 5-HT blockade or depletion resulted in a significant reduction in basal tonic pressures and in the amplitude of phasic contractions, which suggested that serotonergic neurons may play a physiologic role in the regulation of basal SO motor activity.