The effect of veratridine on the release of catecholamines from the perfused adrenal gland.

1. Experiments on perfused adrenal glands of guinea-pigs were carried out to study the catecholamine output induced by veratridine in the presence of hexamethonium and atropine. 2. Veratridine (10 micrometer to 200 micrometer) caused a dose-dependent increase in catecholamine output. 3. The addition of veratridine to the perfusion medium for a period of 3 min caused an increase in catecholamine output which reached a maximum 5 min to 10 min after withdrawal of the drug. The catecholamine output then gradually declined and reached near resting values within 30 minutes. It was never sustained for a longer period, even when veratridine was infused for 1 hour. 4. Veratridine failed to increase the catecholamine output in the absence of extracellular Ca2+. However, the addition of Ca2+ after an infusion of veratridine (100 micrometer) in the absence of Ca2+ caused an increase in the catecholamine output which was proportional to the concentration of Ca2+ (0.55 mM to 8.8 mM) used. 5. Veratridine did not increase the catecholamine output in the absence of extracellular Na+ ions, NaCl being replaced by equimolar choline chloride or LiCl. Veratridine also failed to evoke catecholamine output in a Na+-free solution in which Na+ was replaced by sucrose; this was the case even in the presence of a high concentration of Ca2+ (8.8 mM). 6. Tetrodotoxin (0.1 micrometer) and excess Mg2+ (20 mM) reversibly inhibited the catecholamine output induced by veratridine. 7. Ouabain (10 micrometer) significantly potentiated the veratridine-induced catecholamine output. 8. It is suggested that Na+-dependent Ca2+ influx as well as voltage-dependent Ca2+ influx mechanisms may be involved in the catecholamine output induced by veratridine.