Activation of human large bowel adenylate cyclase by methylated prostaglandin E2 analogues

The effects of methylated analogues of prostaglandin E2 upon the adenylate cyclase system in human colonic mucosa were tested. 16,16-dimethyl-prostaglandin E2 and 15-(S)-methyl-prostaglandin E2 increased the cyclase system in a dose-related manner. Maximal stimulation (about 250%) of enzyme activity occurred at a prostaglandin analogue concentration of 0.1 g/l. Diarrhea seen in patients treated with these orally effective prostaglandin analogues might in part be explained by activation of large bowel adenylate cyclase which is supposed to play a key role in the secretory process in this organ.