Serotonin activates electrolyte transport via 5-HT2A receptor in rat colonic crypt cells

The aim of this study was to demonstrate that 5-HT activates electrolyte transport directly via 5-HT2A receptor in rat colonic crypt cells. Patch-clamp whole cell recording was performed in isolated crypts to measure the 5-HT-induced changes in electrogenic K+ and Cl- currents. Superfusing 5-HT (10 microM) in the bath solution increased both K+ and Cl- currents, which were antagonized by the presence of ketanserin (1 microM), a selective 5-HT2A antagonist, in the bath solution. Mesulergine (1 microM) a 5-HT2A and 5-HT2C antagonist, had no inhibitory effect. Strong chelation of the intracellular Ca2+ by 5 mM BAPTA inhibited 5-HT-induced currents. 5-HT also failed to activate K+ and C1- currents in the presence of GDPbetaS (0.5 mM) in the pipette solution. Intracellular administration of GTPgammaS (0.1 mM) mimicked the stimulatory effect of 5-HT, that was inhibited by 5 mM BAPTA. H-7 (0.05 mM), an inhibitor of protein kinase C, A, and G, did not affect the currents. These data indicate that a G protein-coupled pathway is involved in the activation of electrolyte secretion via 5-HT2A receptor.