Roles of prostaglandin E-receptor subtypes in gastric and duodenal bicarbonate secretion in rats.
OBJECTIVE
Receptors activated by prostaglandin (PG) E2 are pharmacologically subdivided into four subtypes (EP1-EP4). The EP-receptor subtype(s) involved in stimulation of gastroduodenal HCO3- secretion in rats were investigated.


METHODS
Under urethane anesthesia, a stomach mounted in an ex vivo chamber or a proximal duodenal loop was perfused with saline, and HCO3- secretion was measured using a pH-stat method.


RESULTS
Intravenous PGE2 increased HCO3- secretion by the gastroduodenal mucosa; this action was verapamil sensitive and, only in the duodenum, potentiated by isobutylmethyl xanthine (IBMX). Duodenal HCO3- secretion was stimulated by enprostil, sulprostone (EP1/EP3 agonist), misoprostol (EP2/EP3 agonist), and ONO-NT012 (EP3 agonist) but was not affected by butaprost (EP2 agonist) or 17-phenyl-PGE2 (EP1 agonist). Gastric HCO3- secretion was stimulated by sulprostone, enprostil, and 17-phenyl-PGE2 but not by misoprostol, butaprost, or ONO-NT012. SC-51089 (EP1 antagonist) inhibited the HCO3--stimulatory action of sulprostone only in the stomach. IBMX potentiated the HCO3- response to sulprostone in the duodenum, whereas verapamil reduced the response in both the stomach and duodenum.


CONCLUSIONS
PGE stimulates HCO3- secretion via different EP-receptor subtypes in the stomach and duodenum: in the stomach, EP1 receptors are linked to Ca2+; in the duodenum, EP3 receptors are coupled with both adenosine 3', 5'-cyclic monophosphate and Ca2+.
Takeuchi
K
K
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Japan.
Yagi
K
K
Kato
S
S
Ukawa
H
H
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology; D004386:Duodenum / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D010077:Oxazepines / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000145:classification* / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology
D001639:Bicarbonates; D006834:Hydrazines; D010077:Oxazepines; D011458:Prostaglandins E; D018078:Receptors, Prostaglandin E; C086836:SC 51089; C016767:sulprostone; D014700:Verapamil; D015232:Dinoprostone; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine