Endogenous dopamine and duodenal bicarbonate secretion in humans.
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.
Knutson
L
L
Department of Surgery, University Hospital, Uppsala, Sweden.
Knutson
T W
TW
Flemström
G
G
D000328:Adult; D001639:Bicarbonates / Q000378:metabolism*; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D002396:Catechols / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016595:Misoprostol / Q000494:pharmacology; D010422:Pentanones / Q000494:pharmacology
D001639:Bicarbonates; D002396:Catechols; D010422:Pentanones; D016595:Misoprostol; C057364:nitecapone; D002394:Catechol O-Methyltransferase; D015232:Dinoprostone; D004298:Dopamine