EFFECTS OF METHOXYVERAPAMIL ON THE STIMULATION BY CA2+, SR2+ AND BA2+ AND ON THE INHIBITION BY MG2+ OF CATECHOLAMINE RELEASE FROM THE ADRENAL-MEDULLA

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. Methoxyverapamil (D600) at a concentration of 3 × 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+. Mg2+ (10 to 20 mm) blocked the release induced by Na+‐deprivation; however, this inhibitory effect of Mg2+ was not modified by D600. 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. 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 its inhibitory effect at an extracellular site. 1979 British Pharmacological Society