Acid and isoproterenol cause serotonin release by acting on opposite surfaces of duodenal mucosa.
Although most bodily serotonin (5-HT) is stored in intestinal enterochromaffin (EC) cells, the mechanism of its release is only now being elucidated. It has previously been reported that such stimuli as luminal acidification or exposure of both sides of a rabbit duodenal mucosal sheet to certain autonomic agonists stimulate release from the mucosal surface in the Ussing chamber model. The hypothesis in the present study is that acid acts only on the mucosal surface, whereas neural receptor agonists and antagonists act specifically on the serosal surface, as would be predicted by the location of acid in the gut lumen and nerve terminals at the bases of the EC cells. 5-HT release was measured by radioimmunoassay from the mucosal surface bathing solution. Duodenal mucosal sheets were exposed separately on the mucosal or serosal surfaces to acid (citric phosphate buffer, pH 5) or to isoproterenol (10(-5) M). The effect of atropine (10(-6) M) and propranolol (10(-6) M) on acid-stimulated mucosal release was studied by combining luminal acid stimulation with one of these antagonists, on either the mucosal or serosal surface. The results demonstrate significant (P less than 0.01) mucosal serotonin release (56 +/- 9 ng cm-2 hr-1) only with mucosal acidification. On the other hand, isoproterenol causes significant (P less than 0.05) serotonin release (12.4 +/- 3 ng cm-2 hr-1) only when introduced onto the serosal surface. Finally, the antagonists, atropine and propranolol, blocked acid-stimulated serotonin release only when added to the serosal surface. Since acid-induced serotonin release has been shown to be partially mediated by cholinergic and beta-adrenergic mechanisms, these findings suggest interconnection of mucosal acid receptors with submucosal neurons which mediate serotonin release by acting on the basal surface of the enterochromaffin cell.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002021:Buffers; D002951:Citrates / Q000494:pharmacology*; D004386:Duodenum; D007413:Intestinal Mucosa / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism*; D013268:Stimulation, Chemical
D002021:Buffers; D002951:Citrates; D012701:Serotonin; D001285:Atropine; D011433:Propranolol; D007545:Isoproterenol