Cyclic AMP and cyclic GMP levels in human colonic mucosa before and during chenodeoxycholic acid therapy.

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Abstract
Previous experimental studies suggest that bile salt-induced colonic fluid secretion is mediated by cyclic[c]AMP. Two biopsy specimens of colonic mucosa were obtained endoscopically before and after different periods of therapy (5, 10 or 15 days), from each of 21 patients receiving chenodeoxycholic acid. A rise of cAMP intracellular levels was found, but only after 5 and 10 days of treatment was the increase statistically significant when compared with basal levels. Similar changes were observed for cGMP, but percentage increases were higher than for cAMP. Initial diarrhea disappeared spontaneously and at 15 days the levels of both cyclic nucleotides were not significantly different from basal levels. Colonic adaptation to increase in luminal bile salt levels apparently is related to changes in intracellular levels of cyclic nucleotides. Not only cAMP, but also cGMP may play an important role in producing bile salt-induced diarrhea in man.