Ionophoretic and inhibitory action of the analgesic, diflunisal, on sarcoplasmic reticulum.
Diflunisal decreased the ATP-dependent transport rate and calcium accumulation by the sarcoplasmic reticulum. Inhibition of calcium transport by diflunisal was pH dependent, and a pKa of 6.7 to 6.9 was observed for the carboxylic acid group. In sealed sarcoplasmic reticulum vesicles, diflunisal at concentrations below 1 mM increased the rate of Ca2+-dependent hydrolysis of ATP; above 1 mM, the Ca2+-ATPase activity was inhibited. In purified Ca2+-ATPase, diflunisal acted only as an inhibitor. Methylation of the phenolic group of diflunisal eliminated both its analgesic and ionophoretic properties.
Holguín
J A
JA
Departamento de Bioquímica, Instituto Nacional de Cardiología, México, D.F. México.
D000818:Animals; D002118:Calcium; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D004061:Diflunisal / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007476:Ionophores; D010147:Pain Measurement; D011817:Rabbits; D012459:Salicylates / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects*; D013324:Strontium; D013329:Structure-Activity Relationship
D007476:Ionophores; D012459:Salicylates; D004061:Diflunisal; D000252:Calcium-Transporting ATPases; D002118:Calcium; D013324:Strontium