Karaki H, Nakagawa H, Urakawa N
Eur J Pharmacol. 1984 Jun 1;101(3-4):177-83. doi: 10.1016/0014-2999(84)90154-7.
The effects of several organic Ca antagonists and putative calmodulin antagonists on the release of [3H]noradrenaline from rabbit aorta were examined. A 65.4 mM K solution and electrical stimulation induced a Ca-dependent increase in the 3H-efflux from the adventitial layer (containing nerve terminals) but not from the media-intimal layer. Verapamil, D600, N-(6-aminohexyl)-5-chloro-l-naphthalenesulphonamide (W-7) and N2-dansyl-L-arginine-4-t-butylpiperidine amide (TI 233), in the concentration of 10(-5) M, did not inhibit the increase in 3H-efflux. A high concentration (2 X 10(-4) M) of verapamil induced a Ca-independent increase in the 3H-efflux from the adventitia but not from the media-intimal layer. D600, diltiazem, W-7 and TI233, in the concentration of 2 X 10(-4) M, also increased the 3H-efflux; 65.4 mM K, added in the presence of 2 X 10(-4) M verapamil or W-7, produced no further increase in 3H-efflux. The 3H-efflux evoked by electrical stimulation was only partially inhibited by 2 X 10(-4) M verapamil. It is suggested that the evoked release of noradrenaline in rabbit aorta is relatively insensitive to organic Ca antagonists and calmodulin antagonists, and that high concentrations of these inhibitors themselves release noradrenaline by a mechanism independent of external Ca.
研究了几种有机钙拮抗剂和假定的钙调蛋白拮抗剂对兔主动脉中[3H]去甲肾上腺素释放的影响。65.4 mM钾溶液和电刺激可诱导外膜层（含神经末梢）的3H外流呈钙依赖性增加，但中膜-内膜层则无此现象。维拉帕米、D600、N-(6-氨基己基)-5-氯-1-萘磺酰胺（W-7）和N2-丹磺酰-L-精氨酸-4-叔丁基哌啶酰胺（TI 233），浓度为10(-5) M时，并未抑制3H外流的增加。高浓度（2×10(-4) M）的维拉帕米可诱导外膜层的3H外流呈钙非依赖性增加，但中膜-内膜层则无此现象。D600、地尔硫卓、W-7和TI233，浓度为2×10(-4) M时，也可增加3H外流；在2×10(-4) M维拉帕米或W-7存在的情况下加入65.4 mM钾，3H外流不会进一步增加。电刺激诱发的3H外流仅被2×10(-4) M维拉帕米部分抑制。提示兔主动脉中去甲肾上腺素的诱发释放对有机钙拮抗剂和钙调蛋白拮抗剂相对不敏感，且这些抑制剂的高浓度本身可通过一种不依赖于细胞外钙的机制释放去甲肾上腺素。
