BACKGROUND: Catechol-O-methyltransferase (COMT) inhibition prevents tissue degradation of catecholamines including dopamine. This study was undertaken to investigate the effect of intraluminal nitecapone, a peripherally acting COMT inhibitor, on duodenal mucosal bicarbonate secretion in humans and to compare the effect with that of the prostaglandin E1 analogue misoprostol. METHODS: The duodenal bulb was isolated by means of a three-balloon six-channel tube as previously described. Basal bicarbonate secretion and secretion after intraluminal administration of 30 and 150 mg nitecapone were determined in 11 healthy subjects. In 7 of these subjects, effects of intraluminal administration of 30 and 150 micrograms of misoprostol were studied in a second experiment. RESULTS: Even the lower dose of misoprostol increased duodenal bicarbonate secretion from 121 +/- 12 to 221 +/- 36 and the lower dose of nitecapone from 149 +/- 18 to 277 +/- 48 microEq.cm-1 x h-1, respectively (P < 0.05). With 150 micrograms of misoprostol or 150 mg of nitecapone there was a further increase in secretion to 296 +/- 33 (P < 0.01) and 421 +/- 36 (P < 0.001) microEq.cm-1 x h-1, respectively. The rise in bicarbonate secretion in response to nitecapone was associated with some increase in the release of prostaglandin E2 to the luminal perfusate. CONCLUSIONS: It seems likely that peripheral COMT inhibition increases duodenal mucosal bicarbonate secretion and protection by inhibition of mucosal degradation of dopamine, an increase similar in magnitude to that obtained by a prostaglandin E1 analogue.
BACKGROUND:Catechol-O-methyltransferase (COMT) inhibition prevents tissue degradation of catecholamines including dopamine. This study was undertaken to investigate the effect of intraluminal nitecapone, a peripherally acting COMT inhibitor, on duodenal mucosal bicarbonate secretion in humans and to compare the effect with that of the prostaglandin E1 analogue misoprostol. METHODS: The duodenal bulb was isolated by means of a three-balloon six-channel tube as previously described. Basal bicarbonate secretion and secretion after intraluminal administration of 30 and 150 mg nitecapone were determined in 11 healthy subjects. In 7 of these subjects, effects of intraluminal administration of 30 and 150 micrograms of misoprostol were studied in a second experiment. RESULTS: Even the lower dose of misoprostol increased duodenal bicarbonate secretion from 121 +/- 12 to 221 +/- 36 and the lower dose of nitecapone from 149 +/- 18 to 277 +/- 48 microEq.cm-1 x h-1, respectively (P < 0.05). With 150 micrograms of misoprostol or 150 mg of nitecapone there was a further increase in secretion to 296 +/- 33 (P < 0.01) and 421 +/- 36 (P < 0.001) microEq.cm-1 x h-1, respectively. The rise in bicarbonate secretion in response to nitecapone was associated with some increase in the release of prostaglandin E2 to the luminal perfusate. CONCLUSIONS: It seems likely that peripheral COMT inhibition increases duodenal mucosal bicarbonate secretion and protection by inhibition of mucosal degradation of dopamine, an increase similar in magnitude to that obtained by a prostaglandin E1 analogue.