Synergism between calcium-mediated and cyclic AMP-mediated activation of chloride secretion in isolated guinea pig distal colon.

Synergistic effects of Ca2+-mediated secretagogues and cyclic AMP-mediated secretagogues on Cl- secretion by guinea pig distal colon were studied in vitro using Ussing chambers. Short-circuit current (Isc) and bidirectional fluxes of 22Na+ and 36Cl- were measured. Bethanechol (10(-4) M, a Ca2+-mediated secretagogue) caused an increase in Isc, which was enhanced 4-20 fold when the tissue was pretreated with prostaglandin E2 (10(-7)-10(-6) M), vasoactive intestinal polypeptide (5 x 10(-9)-10(-8) M) (cyclic AMP-mediated secretagogues), or 8-bromocyclic AMP (5 x 10(-4)-2 x 10(-3) M). Measurement of 36Cl flux showed that the increase in Isc in the presence of both 8-bromocyclic AMP and bethanechol resulted principally from increased Cl- secretion. On the other hand, the net absorptive flux of 22Na was not influenced under these conditions. Potentiation of the increase in Isc was also elicited by the combination of A23187 (5 x 10(-6) M) and 8-bromocyclic AMP (10(-3) M). The results are consistent with the notion that simultaneous activation of the cyclic AMP-mediated and Ca2+-mediated systems produces a synergistic increase in colonic Cl- secretion.