On the role of substance P and serotonin in the pyloric motor control. An experimental study in cat and rat.

Vagal nerve stimulation caused a release of substance P (SP) and serotonin (5-HT) into the feline portal circulation. Both substances are gut spasmogens and were demonstrated in gut nerves by immunocytochemistry. In anesthetized cats gastric and pyloric motility were studied simultaneously at stimulation with SP or 5-HT via the splenic artery or at stimulation of the extrinsic nerves to evaluate their role in the motor control of these regions. The vagally induced pyloric contraction was noncholinergic and nonadrenergic but sensitive to hexamethonium in contrast to the cholinergic gastric contraction, which was resistant to ganglionic blockade. Splanchnic nerve stimulation caused relaxatory gastropyloric responses; the gastric relaxation was sensitive to adrenergic or ganglionic blockade in contrast to the pyloric relaxation. Infrequent contractile responses were seen, which were antagonized by atropine. Injection of SP via the splenic artery elicited contractile gastropyloric responses, which were sensitive to atropine and an antagonistic SP-analogue (SPA) but resistant to hexamethonium, indicating SP activating a final cholinergic neuron. The vagally induced pyloric contraction was resistant to atropine but sensitive to SPA and hexamethonium, indicating involvement of SP in the activation of preganglionic neurons as well. Involvement of SP in a vagal afferent mechanism is possible, since heat activation of the distal end of the divided vagal nerve induced a gastric contraction, sensitive to atropine and SPA but not to ganglionic blockade, indicating antidromic activation of SP afferents which via axon collaterals excite cholinergic neurons. A regional difference between stomach and pylorus was suggested by the different motor responses after pharmacological blockade, heat-activation or i.a. injection of capsaicin. The contractile pyloric responses to 5-HT were antagonized by peripheral blockade of 5-HT2 receptors. However, such blockade did not influence the motor responses to extrinsic nerve stimulation, suggesting that 5-HT is not essential for the mediation of these responses. The contractile responses to SP or 5-HT were studied in vitro in antral and pyloric strips from the rat. These responses were antagonized by SPA or SP tachyphylaxis and peripheral blockade of 5-HT2 receptors respectively. The responses were not reduced by tetrodotoxin, indicating main activation of muscular receptors. However, the contractile responses were reduced by atropine or hexamethonium, except the SP-induced pyloric contraction, which was atropine-sensitive but hexamethonium-resistant.(ABSTRACT TRUNCATED AT 400 WORDS)