Stimulation of gastric bicarbonate secretion by an analog of thyrotropin-releasing hormone, YM-14673, in the rat.
The effects of YM-14673, a thyrotropin-releasing hormone analog, on gastric alkaline secretion were investigated in the anesthetized rat pretreated with omeprazole (60 mg/kg, intraperitoneally) by measuring the luminal pH, transmucosal PD and HCO3- output. The whole stomach was perfused at a flow rate of 0.7 ml/min with saline (pH 4.5) in the absence of acid secretion, the pH of the perfusate and PD were continuously monitored and the HCO3- output was measured as acid-neutralizing capacity by back-titration of the perfusate to pH 4.5. YM-14673, given intravenously at the doses (0.1-1 mg/kg) that stimulated acid secretion, increased the pH and HCO3- output in a dose-dependent fashion, but did not significantly affect the PD. Prostaglandin E2 (1 mg/kg) elevated the pH and HCO3- output with concomitant decrease in the PD, whereas carbachol (4 micrograms/kg), similar to YM-14673, produced an increase of the pH and HCO3- output with no change in the PD. The net HCO3- output (4.3 +/- 0.3 muEq) induced by 0.3 mg/kg of YM-14673 was about 60 and 150% of that induced by prostaglandin E2 and carbachol, respectively. The increased pH and HCO3- responses caused by YM-14673 were almost completely abolished by vagotomy, significantly inhibited by atropine (0.3 mg/kg, intravenously) and indomethacin (5 mg/kg, subcutaneously) but not affected by pirenzepine (1 mg/kg, intravenously). These results suggest that YM-14673, a thyrotropin-releasing hormone analog, produced vagally mediated HCO3- secretion in the rat stomach, and the mechanism may involve the cholinergic system, which is mediated with muscarinic M2 receptors and interacts with endogenous prostaglandins.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Ueshima
K
K
Okabe
S
S
D000818:Animals; D001384:Azetidines / Q000494:pharmacology*; D001639:Bicarbonates / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology*; D004347:Drug Interactions; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D008297:Male; D009853:Omeprazole / Q000494:pharmacology; D051381:Rats; D013270:Stomach / Q000187:drug effects*; D014628:Vagotomy
D001384:Azetidines; D001639:Bicarbonates; D004151:Dipeptides; C054995:azetirelin; D002217:Carbachol; D015232:Dinoprostone; D009853:Omeprazole