Effects of methoxyverapamil on the stimulation by Ca2+, Sr2+ and Ba2+ and on the inhibition by Mg2+ of catecholamine release from the adrenal medulla.

1 Bovine adrenal glands were perfused with Ca2+-free Locke solution and catecholamine release was induced either by the introduction of Ca2+, Sr2+ or Ba2+ into the perfusion fluid or by the substitution of Na+ by an osmotically equivalent amount of sucrose. 2 Methoxyverapamil (D600) at a concentration of 3 X 10(-4) M blocked the release of catecholamines in response to Ca2+, Sr2+ or Ba2+ stimulation but failed to block the release evoked by the omission of Na+. 3 Mg2+ (10 to 20 mM) blocked the release induced by Na+-deprivation; however, this inhibitory effect of Mg2+ was not modified by D600. 4 D600 blocked the increase in the efflux of 45Ca from the perfused gland induced by the introduction of Ca2+ into the perfusion fluid and blocked the uptake of 45Ca into adrenal medullary slices induced by K+ depolarization. 5 The results suggest that Ca2+, Sr2+ and Ba2+ may enter the chromaffin cell through the same channel and that this channel is blocked by D600. Mg2+ may enter the cell through the same Ca2+ channel but with a high rate of permeation or it may enter through a channel which is resistant to D600. Alternatively, Mg2+ may exert this inhibitory effect at an extracellular site.