Effect of YM-14673, an analogue of thyrotropin-releasing hormone, on duodenal bicarbonate secretion in the rat.
The effects of YM-14673, an analogue of thyrotropin-releasing hormone, on duodenal HCO3- secretion were characterized in comparison with those of prostaglandin E2 and carbachol in anesthetized rats. The proximal duodenum was perfused with saline (pH 4.5), the pH of the perfusate and of the transmucosal potential difference were continuously monitored, and HCO3- output was determined by back-titration of the perfusate and by pH change. YM-14673 (0.1, 0.3 and 1 mg/kg) increased these parameters in a dose-related manner; the total HCO3- output at 1 mg/kg (5.8 +/- 0.7 mumol) was about 50% of that induced by prostaglandin E2 (1 mg/kg, i.v.) and 2 times greater than that induced by carbachol (4 micrograms/kg, i.v.). These responses, induced by YM-14673, were almost completely blocked by bilateral vagotomy and significantly inhibited by atropine (0.3 mg/kg, i.v.) or cyclooxygenase inhibitors, such as indomethacin (5 mg/kg, s.c.) and acetylsalicylic acid (40 mg/kg, s.c.), but not affected by pirenzepine (1 mg/kg, i.v.), a selective M1 antagonist. None of the latter agents had any effect on the HCO3(-)-stimulating action of prostaglandin E2, while the carbachol-induced HCO3- output was significantly reduced by atropine. These results suggest that YM-14673 induces the vagal-dependent HCO3- secretion in the rat duodenum and that this mechanism is mediated by muscarinic cholinoceptors, excluding the M1-subtype, and may involve endogenous prostaglandins.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Niida
H
H
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*; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives*; D014628:Vagotomy
D001384:Azetidines; D001639:Bicarbonates; D004151:Dipeptides; D010276:Parasympatholytics; D013973:Thyrotropin-Releasing Hormone; C054995:azetirelin; D002217:Carbachol; D015232:Dinoprostone; D007213:Indomethacin