Roles of 5-HT receptors in the release and action of secretin on pancreatic secretion in rats.
5-Hydroxytryptamine (serotonin, 5-HT) is a hormone and neurotransmitter regulating gastrointestinal functions. 5-HT receptors are widely distributed in gastrointestinal mucosa and the enteric nervous system. Duodenal acidification stimulates not only the release of both 5-HT and secretin but also pancreatic exocrine secretion. We investigated the effect of 5-HT receptor antagonists on the release of secretin and pancreatic secretion of water and bicarbonate induced by duodenal acidification in anesthetized rats. Both the 5-HT(2) receptor antagonist ketanserin and the 5-HT(3) receptor antagonist ondansetron at 1-100 microg/kg dose-dependently inhibited acid-induced increases in plasma secretin concentration and pancreatic exocrine secretion. Neither the 5-HT(1) receptor antagonists pindolol and 5-HTP-DP nor the 5-HT(4) receptor antagonist SDZ-205,557 affected acid-evoked release of secretin or pancreatic secretion. None of the 5-HT receptor antagonists affected basal pancreatic secretion or plasma secretin concentration. Ketanserin or ondansetron at 10 microg/kg or a combination of both suppressed the pancreatic secretion in response to intravenous secretin at 2.5 and 5 pmol x kg(-1) x h(-1) by 55-75%, but not at 10 pmol x kg(-1) x h(-1). Atropine (50 microg/kg) significantly attenuated the inhibitory effect of ketanserin on pancreatic secretion but not on the release of secretin. These observations suggest that 5-HT(2) and 5-HT(3) receptors mediate duodenal acidification-induced release of secretin and pancreatic secretion of fluid and bicarbonate. Also, regulation of pancreatic exocrine secretion through 5-HT(2) receptors may involve a cholinergic pathway in the rat.
Li
J P
JP
Konar Center for Digestive and Liver Diseases, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA.
Chang
T M
TM
Chey
W Y
WY
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004386:Duodenum / Q000378:metabolism; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D017294:Ondansetron / Q000494:pharmacology; D010179:Pancreas / Q000378:metabolism*; D010189:Pancreatic Juice / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D012633:Secretin / Q000378:metabolism* / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D018727:Muscarinic Antagonists; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012633:Secretin; D017294:Ondansetron; D001285:Atropine; D007650:Ketanserin