β-Adrenoceptors on duodenal mucosal cells mediate venous serotonin release

Abstract

We have previously documented predominant intraluminal release of serotonin (5-HT) following activation of muscarinic receptors on enterochromaffin cells. Gronstad et al. reported that portal venous release of 5-HT in response to vagal stimulation was mediated by β-adrenergic receptors. The purpose of this study was to determine whether 5-HT release induced by the β-adrenergic agonist, isoproterenol, is mediated by enteric nerves or is a direct action at the enterochromaff in cell level. We mounted rabbit duodenal mucosal sheets stripped of muscularis in modified Ussing chambers and measured release of 5-HT in response to 10 −5 M isoproterenol, in the presence and absence of the neural conduction blocker tetrotoxin, 10 −6 M. Serotonin was measured in the buffer bathing the mucosal and submucosal surfaces by HPLC. In the presence of isoproterenol, total (mucosal and submucosal) 5-HT release (21.0 ± 4.9 ng/cm 2/45 min) was significantly ( P < 0.05) greater than that in untreated controls (7.8 ± 2.7 ng/cm 2/45 min); release was predominantly toward the submucosal surface. In the presence of tetrodotoxin alone, net 5-HT release was significantly ( P < 0.05) increased to 12.8 ± 2.8 ng/cm 2/45 min. In tetrodotoxin-treated mucosa, isoproterenol increased 5-HT release to 28.6 ± 5.3 ng/cm 2/45 min which was significantly greater ( P < 0.05) than that with tetrodotoxin alone. Since 5-HT release was increased even in the presence of neural blockade, these results suggest that activation of β-adrenergic receptors on or near enterochromaffin cells induces release of 5-HT predominantly toward the submucosal surface.