Mechanisms of antisecretory action of intragastric FPL-52694: a mast cell stabilizer in anesthetized rats.
Mechanisms of antisecretory action of intragastric FPL-52694, a mast cell stabilizer, were investigated in anesthetized rats. In Schild's rat preparation, intravenous FPL-52694 (10 mg/kg) significantly suppressed acid secretion in response to only tetragastrin (20 micrograms/kg, i.v.) (42.1 +/- 19.4%), while intragastric application of FPL-52694 (100 mg/kg) for 30 min produced a marked, unequivocal inhibition (over 70%) in acid secretory responses to histamine (1 mg/kg, i.v.) and carbachol (2.5 micrograms/kg, i.v.) as well as tetragastrin. The inhibitory effect of intragastric FPL-52694 was confirmed in the lumen-perfused rats, where acid secretion (24-25 mumol/10 min) induced by intravenous infusion of histamine (8 mg/kg/h) was abolished for 1 h after exposure of the stomach for 30 min to this agent. Inhibition of histamine-stimulated acid secretion by intragastric FPL-52694 was much greater and lasted longer (2 h) as compared with xylocaine (4% solution), but significantly mitigated by pretreatment of the rats with subcutaneous administration of indomethacin (3 mg/kg). Furthermore, application of FPL-52694 but not of xylocaine to the stomach caused a reduction of transmucosal potential difference, an increase of luminal appearance of HCO-3 (1-2 mumol/10 min), and an enhancement of H+ back-diffusion, although no damage was appreciated in the mucosa. These results suggest that antisecretory action of intragastric FPL-52694 may involve local mechanisms such as neutralization of acid with HCO-3, a loss of acid due to H+ back-diffusion, and inhibition of acid production mediated by endogenous prostaglandins, but is not related to the local anesthetic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
D000758:Anesthesia; D000818:Animals; D002867:Chromones / Q000008:administration & dosage / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism*; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism
D002867:Chromones; C029061:FPL-52694; D008012:Lidocaine; D012964:Sodium; D011188:Potassium