Carbocyclic thromboxane A2 inhibits Cl- absorption in the rat colon

The effect of carbocyclic thromboxane A2 (CTXA2) on short-circuit current (Isc) was studied in two preparations of the rat colon descendens, one with and one without the submucosal plexus. In both preparations, CTXA2 (10(-7)-5 x 10(-6) mol.l-1) increased Isc concentration-dependently. Its action was not inhibited by the neurotoxin, tetrodotoxin, or by indomethacin, indicating a direct action on the epithelium. The increase in Isc was dependent on the presence of Cl- and HCO3- anions in the medium, but it was not affected by inhibitors of Cl-secretion such as furosemide or a Cl- channel blocker. Measurements of the unidirectional fluxes of Na+ and Cl-revealed that the dominant action of CTXA2 was an inhibition of the mucosa to serosa flux of Cl-. The action of CTXA2 was prevented by pretreatment with the thromboxane receptor blocker, SK&F 88046. It was also inhibited by TMB-8, a substance preventing the release of Ca2+ from intracellular stores, but its effect was not dependent on the presence of extracellular Ca2+. The results indicate that thromboxanes can modulate Cl-transport through the colonic epithelium by a mechanism dependent on intracellular Ca2+.