Effects of calcium antagonists on release of [3H]noradrenaline in rabbit aorta

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.