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

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Abstract
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 (10-4M, a Ca2+-mediated secretagogue) caused an increase in Isc, which was enhanced 4-20 fold when the tissue was pretreated with prostaglandin E2 (10-7-10-6M), vasoactive intestinal polypeptide (5×10-9-10-8M) (cyclic AMP-mediated secretagogues), or 8-bromocyclic AMP (5×10-4-2×10-3M). 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 (5×10-6M) and 8-bromocyclic AMP (10-3M). 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.

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