FAILURE TO REVERSE CHOLERA TOXIN INDUCED INTESTINAL SECRETION BY AGENTS WHICH DECREASE MUCOSAL CAMP

The feasibility of reducing intestinal secretion by the use of agents which decrease intestinal mucosal c[cyclic]AMP concentration was investigated in the weanling pig and the rabbit. Three different agents for decreasing mucosal cAMP concentration were studied. The cyclic nucleotide phosphodiesterase activator, imidazole, significantly reduced mucosal cAMP concentrations only in the weanling pig. Intraluminal 2''-deoxyadenosine-3''-AMP inhibited adenylate cyclase and caused a decrease in mucosal cAMP concentration in the pig and the rabbit. The introduction of the heat-stable enterotoxin of Escherichia coli into pig jejunal segments gave lowered mucosal cAMP concentrations. While these 3 agents effectively reduced cAMP concentrations in intestinal mucosa, they were ineffective in reducing the net fluid secretory effects of cholera toxin. Secretion caused by cholera toxin apparently persists independent of the temporary changes in cAMP concentration which can be induced by pharmacological agents.