5-hydroxytryptamine strongly inhibits fluid secretion in guinea pig pancreatic duct cells
Atsushi Suzuki, Satoru Naruse, Motoji Kitagawa, Hiroshi Ishiguro, Toshiyuki Yoshikawa, Shigeru B.H. Ko, Akiko Yamamoto, Hiroyuki Hamada, Tetsuo Hayakawa
Atsushi Suzuki, Satoru Naruse, Motoji Kitagawa, Hiroshi Ishiguro, Toshiyuki Yoshikawa, Shigeru B.H. Ko, Akiko Yamamoto, Hiroyuki Hamada, Tetsuo Hayakawa
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5-hydroxytryptamine strongly inhibits fluid secretion in guinea pig pancreatic duct cells

Abstract

We studied the distribution of 5-hydroxytryptamine– (5-HT-) containing cells in the guinea pig pancreas and examined the effects of 5-HT on fluid secretion by interlobular pancreatic ducts. The 5-HT–immunoreactive cells with morphological characteristics of enterochromaffin (EC) cells were scattered throughout the duct system and were enriched in islets of Langerhans. The fluid secretory rate in the isolated interlobular ducts was measured by videomicroscopy. Basolateral applications of 5-HT strongly but reversibly reduced HCO3-dependent, as well as secretin- and acetylcholine- (ACh-) stimulated, fluid secretion, whereas 5-HT applied into the lumen had no such effects. Secretin-stimulated fluid secretion could be inhibited by a 5-HT3 receptor agonist, but not by agonists of the 5-HT1, 5-HT2, or 5-HT4 receptors. Under the stimulation with secretin, 5-HT decreased the intracellular pH (pHi) and reduced the rate of pHi recovery after acid loading with NH4+, suggesting that 5-HT inhibits the intracellular accumulation of HCO3–. The elevation of intraductal pressure in vivo reduced secretin-stimulated fluid secretion, an effect that could be attenuated by a 5-HT3 receptor antagonist. Thus, 5-HT, acting through basolateral 5-HT3 receptors, strongly inhibits spontaneous, secretin-, and ACh-stimulated fluid secretion by guinea pig pancreatic ducts. 5-HT released from pancreatic ductal EC cells on elevation of the intraductal pressure may regulate fluid secretion of neighboring duct cells in a paracrine fashion.

Authors

Atsushi Suzuki, Satoru Naruse, Motoji Kitagawa, Hiroshi Ishiguro, Toshiyuki Yoshikawa, Shigeru B.H. Ko, Akiko Yamamoto, Hiroyuki Hamada, Tetsuo Hayakawa

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Effects of luminal 5-HT on fluid secretion. The lumen of the cultured du...
Effects of luminal 5-HT on fluid secretion. The lumen of the cultured ducts was micropunctured and the luminal fluid was replaced by the HEPES-buffered solution with or without 5-HT (1 μM). The ducts were initially superfused with HEPES-buffered solution for 5 minutes. The bath solution was switched to the HCO3–-CO2-buffered solution. After a 6-minute period, 1 nM secretin was added to the bath. (a) The fluid secretory rate in ducts injected with 5-HT (1 μM). Mean ± SEM of four experiments. (b) Spontaneous (HCO3–-CO2–dependent) and secretin-stimulated (1 nM) fluid secretion in the absence (filled bars) and presence (open bars) of luminal 5-HT (1 μM). Mean ± SEM of four experiments.