Veratridine and Ouabain Stimulate Calcium-Dependent Prolactin Release*

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Abstract
The effects were investigated of veratridine, a Na+ channel activator, and ouabain, an inhibitor of Na+-K+-ATPase, on short term (1 h) PRL [prolactin] release from primary cultures of rat anterior pituitary cells and from the rat anterior pituitary cell line GH4C1 in culture. Both compounds should increase intracellular Na+. Veratridine (20-500 .mu.M) and ouabain (0.1-3 mM) stimulated PRL release from normal cells. The stimulation was inhibited by the omission of Ca2+ from the release buffer or by preincubation with the Ca channel blocker D600 [methoxyverapamil] (20-500 .mu.M), suggesting a role for Ca2+ in the action of these compounds. Ouabain (1 mM), but not veratridine (200 .mu.M), stimulated PRL release from GH4C1 cells, an effect that was also inhibited by Ca channel blockers. In the presence of the dopaminergic agonist bromocriptine (30 nM), the amount of stimulated release by veratridine (200 .mu.M) and ouabain (1 mM), was reduced by 50%. The veratridine effect was only partially inhibited by preincubation of the cells with the Na+ channel blocker tetrodotoxin (1 and 10 .mu.M), but the effect was inhibited completely when Na+ in the buffer was replaced by choline, suggesting that the action of veratridine requires extracellular Na+. Ouabain- and veratridine-stimulated PRL release apparently are largely dependent on Ca2+. Veratridine appears to act through a tetrodotoxin-insensitive mechanism. Stimulation of PRL release by these compounds is similar to that by 50 mM KCl and cAMP in its sensitivity to bromocriptine.