Calcium channel modulators: effects on gastric function.
Calcium is important in stimulus-secretion coupling in the gut. We therefore examined a dihydropyridine (nitrendipine), a phenylalkylamine (verapamil) and a benzothiazepine (diltiazem) calcium channel blocker as well as a calcium channel 'agonist', CGP 28392, in several models of gastric function. Nitrendipine significantly decreased stress-induced gastric lesions, but was far less efficacious against 100% ethanol-induced lesions. The anti-ulcer effects of nitrendipine were not reversible with indomethacin, sodium meclofenamate or N-ethylmaleimide. Nitrendipine also significantly reduced basal gastric acid output. Verapamil significantly reduced stress lesions in an indomethacin and meclofenamate-reversible manner, but worsened ethanol ulcers. Verapamil also decreased basal acid secretion. Diltiazem decreased stress lesions (indomethacin- and meclofenamate-reversible), worsened ethanol lesions and slightly reduced acid secretion. CGP 28392 exerted a modest stress gastroprotective effect, decreased ethanol lesions and reduced slightly basal acid secretion. A possible clinical role for gastric calcium channel blockade is raised by these results.
Glavin
G B
GB
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003080:Cold Temperature; D000431:Ethanol; D005744:Gastric Acid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012149:Restraint, Physical; D013270:Stomach / Q000187:drug effects* / Q000503:physiopathology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000503:physiopathology
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D000431:Ethanol