EFFECT OF SOMATOSTATIN ON CELL-VOLUME, CL CURRENTS, AND TRANSEPITHELIAL CL- TRANSPORT IN RAT DISTAL COLON

Somatostatin (10-(10)-10(-7) mol/l) caused a concentration-dependent increase of the diameter of isolated crypts from the rat distal colon. Cell swelling was restricted to the upper one-third of the crypt and was dependent on the presence of Na+ and Cl- ions, indicating that it was caused by the stimulation of NaC1 absorption by the hormone. Swelling was followed by a regulatory volume decrease, which could be inhibited by K+ and Cl- channel blockers. Also a lipoxygenase inhibitor and a leukotriene D-4 receptor blocker inhibited volume regulation. Whole cell recordings performed in parallel revealed that somatostatin induced a depolarization of the cells at the upper one-third of the crypt but had no effect in the deeper parts of the crypt. This depolarization was concomitant with an increase in Cl- (and partially also HCO3-) conductance and was suppressed by a leukotriene D-4 receptor blocker. In contrast, when Cl- secretion was stimulated by vasoactive intestinal peptide, a secretagogue acting on the adenosine 3',5'-cyclic monophosphate (cAMP) pathway, the effect of somatostatin was reversed from a depolarization into a hyperpolarization, an effect that was also observed in deeper parts of the crypt. Consequently, in crypts stimulated via the cAMP pathway, somatostatin inhibits the activation of apical Cl- channels. Somatostatin also partially inhibited the increase of K+ conductance induced by carbachol, a secretagogue acting on the Ca2+ pathway. Ussing chamber experiments showed that somatostatin caused a concentration-dependent decrease of short-circuit current. This decrease was dependent on the presence of Cl- and HCO3- ions. Measurements of unidirectional ion fluxes indicated that somatostatin stimulated Cl- absorption by an increase of the mucosa-to-serosa flux of this ion. The stimulation of Cl- absorption was completely suppressed by a Cl- channel blocker and by a lipoxygenase inhibitor. Consequently, the activation of a volume/leukotriene-sensitive basolateral Cl- conductance seems to be involved in the stimulation of Cl- absorption by somatostatin.