Effects of W-7 on catecholamine release and 45Ca2+ uptake in cultured adrenal chromaffin cells.
Effects of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin antagonist, on catecholamine (CA) release and 45Ca2+ uptake were studied using cultured bovine adrenal chromaffin cells. W-7 inhibited the carbamylcholine (CCh)-evoked CA release and 45Ca2+ uptake in a concentration-dependent manner. The inhibitory effect of W-7 on CCh-evoked CA release was not overcome either by an increase in extracellular calcium or CCh concentration. Although W-7 inhibited the high K+-evoked CA release and 45Ca2+ uptake, potency of the drug was approximately 50-100 fold less than when inhibiting the CCh-evoked CA release and 45Ca2+ uptake. The inhibitory effects of W-7 were observed both in norepinephrine release and epinephrine release. Moreover, W-7 inhibited the CCh-evoked 45Ca2+ efflux. These results suggest that the inhibition of CA release by W-7 in adrenal chromaffin cells is mainly due to its inhibition of calcium uptake. W-7 may influence the linkage between acetylcholine-receptor and calcium uptake with higher potency than depolarization-dependent calcium entry.
D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002217:Carbachol / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004837:Epinephrine / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D002147:Calmodulin; D002395:Catecholamines; D013449:Sulfonamides; D000001:Calcimycin; C017967:W 7; D011189:Potassium Chloride; D002217:Carbachol; D014700:Verapamil; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine