CYCLIC-AMP AND CA-2+ INTERACTIONS AFFECTING EPITHELIAL CHLORIDE SECRETION IN HUMAN CULTURED COLONIC EPITHELIA

1 Chloride secretion in three types of cultured epithelial monolayers derived from a single human colonic adenocarcinoma was measured in terms of short circuit current. The three cell types were designated HCA-7, Colony 3 and Colony 29. 2 Responses of HCA-7 monolayers to basolaterally applied lysylbradykinin (LBK) (10-1000 nM) or carbachol (1-100 muM) were potentiated by pre-exposure to forskolin (10 muM) for 5 min. Forskolin itself increased short circuit current (SCC), so that the total response to forskolin and LBK or carbachol were non-additive. 3 Colony 3 cells did not respond to LBK on either face but did to carbachol on the basolateral side, while Colony 29 epithelia responded to LBK on both sides and to carbachol and histamine basolaterally. Unlike HCA-7 epithelia, responses iri Colony 3 and Colony 29 epithelia were not potentiated by forskolin, but were attenuated by piroxicam. 4 In the presence of piroxicam, both forskolin and prostaglandin E2 were able to potentiate the action of both LBK and carbachol in Colony 29 epithelia. 5 LBK receptor activation in Colony 29 epithelia is transduced into an increase in intracellular Ca2+ and cyclic AMP, while in HCA-7 epithelia there is only an increase in intracellular Ca2+ (Ca(i)). These conclusions are considered to apply to both apical and basolateral kinin receptors. 6 It is shown that forskolin has no effect on the elevation of Ca2+ by LBK in either HCA-7 or Colony 29 cells. 7 It is concluded that potentiation of agonist responses occurs when cyclic AMP is raised at the time that intracellular Ca2+ increases. No potentiation of LBK or carbachol by forskolin occurs in Colony 29 monolayers as these agonists increase cyclic AMP via eicosanoid production.