Sasakawa N, Kumakura K, Yamamoto S, Kato R
Life Sci. 1983 Nov 14;33(20):2017-24. doi: 10.1016/0024-3205(83)90741-5.
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.
利用培养的牛肾上腺嗜铬细胞，研究了钙调蛋白拮抗剂N-(6-氨基己基)-5-氯-1-萘磺酰胺（W-7）对儿茶酚胺（CA）释放及45Ca2+摄取的影响。W-7以浓度依赖的方式抑制氨甲酰胆碱（CCh）诱发的CA释放及45Ca2+摄取。细胞外钙浓度或CCh浓度的增加均不能克服W-7对CCh诱发的CA释放的抑制作用。虽然W-7抑制高钾诱发的CA释放及45Ca2+摄取，但其效力比抑制CCh诱发的CA释放及45Ca2+摄取时约低50-100倍。在去甲肾上腺素释放和肾上腺素释放中均观察到W-7的抑制作用。此外，W-7抑制CCh诱发的45Ca2+外流。这些结果提示，W-7对肾上腺嗜铬细胞CA释放的抑制作用主要是由于其对钙摄取的抑制。W-7可能以比去极化依赖性钙内流更高的效力影响乙酰胆碱受体与钙摄取之间的联系。
