Calcium channel blockers and prostaglandin generation by gastric surface epithelial cells.
We investigated the effects of calcium channel blockers on generation of prostaglandin (PG) E2 and 6-keto PGF1 alpha by gastric mucosal surface epithelium. Surface epithelial cells (SEC) isolated from rat gastric mucosa were incubated with either verapamil (1 or 10 micrograms/ml), diltiazem (2.5 or 25 micrograms/ml) or nifedipine (2.5 or 25 micrograms/ml) for 30 min at 37 degrees C in calcium containing or calcium-free medium. Verapamil (both doses) significantly increased PGE2 and 6-keto PGF1 alpha generation by the surface epithelial cells but only in calcium containing medium. Diltiazem did not affect PG generation in calcium containing nor calcium-free medium. Nifedipine 25 micrograms/ml decreased PGE2 but increased 6-keto PGF1 alpha generation. The inhibitory effect of nifedipine on PGE2 generation was abolished in calcium-free medium, while the calmodulin antagonist did not affect verapamil-induced increase in PG generation.
Fukuda
T
T
Gastroenterology Section, Veterans Administration Medical Center, Long Beach, California 90822.
Arakawa
T
T
Mach
T
T
Durbin
T
T
Tarnawski
A
A
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D004110:Diltiazem / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002147:Calmodulin; D013449:Sulfonamides; D015121:6-Ketoprostaglandin F1 alpha; C017967:W 7; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D015232:Dinoprostone; D002118:Calcium