5-HT induces duodenal mucosal bicarbonate secretion via cAMP- and Ca2+-dependent signaling pathways and 5-HT4 receptors in mice

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 286; no. 3; p. G444
• Main Authors: Tuo, Bi-Guang, Sellers, Zachary, Paulus, Petra, Barrett, Kim E, Isenberg, Jon I
• Format: Journal Article
• Language: English
• Published: United States 01-03-2004
• Subjects: Animals; Bicarbonates - metabolism; Calcium Signaling - physiology; Cyclic AMP - physiology; Dioxanes - pharmacology; Dose-Response Relationship, Drug; Duodenum - drug effects; Duodenum - metabolism; Intestinal Mucosa - metabolism; Ion Channels - drug effects; Ion Channels - metabolism; Mice; Piperidines - pharmacology; Receptors, Serotonin, 5-HT4 - drug effects; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; Serotonin - pharmacology; Serotonin Receptor Agonists - pharmacology; Signal Transduction - drug effects; Sulfonamides - pharmacology
• ISSN: 0193-1857
• DOI: 10.1152/ajpgi.00105.2003

In previous studies, we have found that 5-hydroxytryptamine (5-HT) is a potent stimulant of duodenal mucosal bicarbonate secretion (DMBS) in mice. The aim of the present study was to determine the intracellular signaling pathways and 5-HT receptor subtypes involved in 5-HT-induced DMBS. Bicarbonate secretion by murine duodenal mucosa was examined in vitro in Ussing chambers. 5-HT receptor involvement in DMBS was inferred from pharmacological studies by using selective 5-HT receptor antagonists and agonists. The expression of 5-HT(4) receptor mRNA in duodenal mucosa and epithelial cells was analyzed by RT-PCR. cAMP-dependent signaling pathway inhibitors MDL-12330A, Rp-cAMP, and H-89 and Ca(2+)-dependent signaling pathway inhibitors verapamil and W-13 markedly reduced 5-HT-stimulated duodenal bicarbonate secretion and short-circuit current (I(sc)), whereas cGMP-dependent signaling pathway inhibitors NS-2028 and KT-5823 failed to alter these responses. Both SB-204070 and high-dose ICS-205930 (selective 5-HT(4) receptor antagonists) markedly inhibited 5-HT-stimulated bicarbonate secretion and I(sc), whereas methiothepine (5-HT(1) receptor antagonist), ketanserin (5-HT(2) receptor antagonist), and a low concentration of ICS-205930 (5-HT(3) receptor antagonist) had no effect. RS-67506 (partial 5-HT(4) receptor agonist) concentration-dependently increased bicarbonate secretion and I(sc), whereas 5-carboxamidotryptamine (5-HT(1) receptor agonist), alpha-methyl-5-HT (5-HT(2) receptor agonist), and phenylbiguanide (5-HT(3) receptor agonist) did not significantly increase bicarbonate secretion or I(sc). RT-PCR analysis confirmed the expression of 5-HT(4) receptor mRNA in murine duodenal mucosa and epithelial cells. These results demonstrate that 5-HT regulates DMBS via both cAMP- and Ca(2+)-dependent signaling pathways and 5-HT(4) receptors located in the duodenal mucosa and/or epithelial cells.