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 NaCl 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 D4 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 D4 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.
Diener
M
M
Institut für Veterinär-Physiologie, Universität Zürich, Switzerland.
Gartmann
V
V
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology; D002712:Chlorides / Q000502:physiology*; D003106:Colon / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D004347:Drug Interactions; D004594:Electrophysiology; D005260:Female; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D013004:Somatostatin / Q000494:pharmacology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D018118:Chloride Channels; D002712:Chlorides; D013757:Tetraethylammonium Compounds; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D019789:Tetraethylammonium; D002217:Carbachol