Peripheral and central involvement of 5-hydroxytryptamine in control of interdigestive migrating contractions by motilin.

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1. In order to study the role 5-hydroxytryptamine in the peripheral action of motilin, the canine stomach was perfused with artificial blood after the stomach was isolated from the donor dog. As a result, motilininduced contractions migrated toward the pyloric ring in the isolated stomach were completely inhibited by treatment of the perfused stomach with a 5-hydroxytryptamine 3 receptor antagonist. It is concluded that 5-hydroxytryptamine is involved in the action of motilin in the isolated stomach. In the same system, it was also found that alpha-adrenergic receptors and the cholinergic neuron were involved in the action of motilin.2. The effects of various receptor antagonists on EM523-induced contractions in the gastrointestinal tract were studied in conscious dogs in which force trasducers were chronically implanted to measure gastrointestinal contractions. EM523, a non-peptide motilin agonist, was found to induce phase III-like contractions in the stomach in a dose-related manner with concomitant increase in the plasma consentration of motilin. The EM523-induced contractions in the stomach were eliminated by pretreatment of dogs with cholinergic and 5-hydroxytryptamine 3 receptor antagonists, and dopamine, but the contractions were not influenced by opiate (mu) receptor antagonist and methysergide. These findings obtained in conscious dogs agree with those found in the isolated stomach.3 In the present study, it was revealed that 5-hydroxytryptamine neuron is involved in the control of contractions in the gastrointestinal tract by motilin, but the relationship between 5-hydroxytryptamine neuron and motilin receptors in the stomach has not been elucidated ; this should be clarified in the future. The role of 5-hydroxytryptamine in the CNS in the control of the interdigestive migrating contractions by motilin has been also studied, but no definite conclusion could be obtained ; further studies are needed.