Beta-adrenoceptors on duodenal mucosal cells mediate venous serotonin release.
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 beta-adrenergic receptors. The purpose of this study was to determine whether 5-HT release induced by the beta-adrenergic agonist, isoproterenol, is mediated by enteric nerves or is a direct action at the enterochromaffin 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/cm2/45 min) was significantly (P less than 0.05) greater than that in untreated controls (7.8 +/- 2.7 ng/cm2/45 min); release was predominantly toward the submucosal surface. In the presence of tetrodotoxin alone, net 5-HT release was significantly (P less than 0.05) increased to 12.8 +/- 2.8 ng/cm2/45 min. In tetrodotoxin-treated mucosa, isoproterenol increased 5-HT release to 28.6 +/- 5.3 ng/cm2/45 min which was significantly greater (P less than 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 beta-adrenergic receptors on or near enterochromaffin cells induces release of 5-HT predominantly toward the submucosal surface.
Kuemmerle
J F
JF
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0161.
Smith
E H
EH
Borum
E H
EH
Kellum
J M
JM
D000818:Animals; D004338:Drug Combinations; D004386:Duodenum / Q000166:cytology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012701:Serotonin / Q000097:blood*; D013779:Tetrodotoxin / Q000494:pharmacology; D014680:Veins
D004338:Drug Combinations; D011943:Receptors, Adrenergic, beta; D012701:Serotonin; D013779:Tetrodotoxin; D007545:Isoproterenol