We studied the distribution of 5-hydroxytryptamine- (5-HT-) containing cell
s in the guinea pig pancreas and examined the effects of 5-HT on fluid secr
etion 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 vid
eomicroscopy. Basolateral applications of 5-HT strongly but reversibly redu
ced HCO3-dependent, as well as secretin- and acetylcholine- (ACh-) stimulat
ed, fluid secretion.,whereas 5-HT applied into the lumen had no such effect
s. Secretin-stimulated fluid secretion could be inhibited by a 5-HT3 recept
or agonist, but not by agonists of the 5-HT1, 5-HT2, or 5-HT4 receptors. Un
der the stimulation with secretin, 5-HT decreased the intracellular pH (pH(
i)) and reduced the rate of pH(i) recovery after acid loading with NH4+, su
ggesting that 5-HT inhibits the intracellular accumulation of HCO3-. The el
evation of intraductal pressure in vivo reduced secretin-stimulated fluid s
ecretion, an effect that could be attenuated by a 5-HT3 receptor antagonist
. Thus, 5-HT3 acting through basolateral 5-HT3 receptors, strongly inhibits
spontaneous, secretin-, and ACh-stimulated fluid secretion by guinea pig p
ancreatic ducts. 5-HT released from pancreatic ductal EC cells on elevation
of the intraductal pressure may regulate fluid secretion of neighboring du
ct cells in a paracrine fashion.