Inhibition of rabbit duodenal bicarbonate secretion by ulcerogenic agents: histamine-dependent and -independent effects.
OBJECTIVE
The gastroduodenal epithelium is protected from acid-peptic damage, in part, by its ability to secrete bicarbonate. Patients with duodenal ulcer disease have impaired proximal duodenal mucosal bicarbonate secretion. We have shown in vitro that histamine inhibits prostaglandin-stimulated bicarbonate secretion in rabbit duodenal mucosa via histamine H2 receptors and enteric nerves. In this study we examined whether the proulcerogenic compounds aspirin or ethanol regulate duodenal bicarbonate secretion and the involvement of histamine.


METHODS
Bicarbonate secretion by rabbit proximal duodenal mucosa was examined in vitro in Ussing chambers.


RESULTS
Aspirin and ethanol decreased basal and prostaglandin-stimulated bicarbonate secretion; the latter effect was specific for prostaglandin. The inhibitory effects of the two ulcerogenic compounds were at least additive. Ranitidine and tetrodotoxin abolished the inhibitory effects on stimulated, but not basal, secretion. Aspirin and ethanol also induced release of duodenal histamine.


CONCLUSIONS
Aspirin and ethanol act by two distinct pathways to impair duodenal bicarbonate secretion. Both agents inhibit basal secretion via a histamine-independent and neurally independent pathway while they inhibit prostaglandin E2-stimulated secretion via histamine release, likely from mast cells, and actions on enteric nerves. Our findings may be of relevance to the understanding and potential treatment of nonsteroidal anti-inflammatory drug-associated mucosal injury.
Myers
C P
CP
Department of Medicine, University of California, San Diego, School of Medicine, 92103-8414, USA.
Hogan
D
D
Yao
B
B
Koss
M
M
Isenberg
J I
JI
Barrett
K E
KE
D000818:Animals; D001241:Aspirin / Q000633:toxicity*; D001639:Bicarbonates / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D004558:Electric Stimulation; D000431:Ethanol / Q000633:toxicity*; D006632:Histamine / Q000502:physiology*; D006636:Histamine Release / Q000187:drug effects; D008297:Male; D011817:Rabbits; D011899:Ranitidine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D001639:Bicarbonates; D000431:Ethanol; D013779:Tetrodotoxin; D006632:Histamine; D011899:Ranitidine; D015232:Dinoprostone; D001241:Aspirin