32 P. INCORPORATION INTO PHOSPHATIDYLINOSITOL IN THE ANTERIOR PITUITARY

The hi vitro effect of dopamine, haloperidol and pimozide on 32p^ incorporation into phosphatidylinositol, phosphatidylcholine and phosphatidylethanolamine by anterior pituitary glands was studied. Dopamine decreased the incorporation of 32p- j n t0 phosphatidylinositol in a dose-related manner without affecting phosphatidyicholine and phosphatidylethanolamine. Haloperidol and pimozide did not modify 32p^ incorporation into these phospholipids by themselves but completely reversed the inhibitory effect of dopamine on phosphatidylinositol. The inhibition of 32pj incorporation into phosphatidyiinositol synthesis in the presence of 500 nM dopamine was significant at 20 min of incubation and maximal at 30 min. The possibility that a decrease in phosphatidylinositol cleavage and turnover may be involved in the inhibitory regulation of prolactin secretion by DA is suggested. It is widely accepted that prolactin is under tonic inhibitory dopaminergic control (1,2). Dopamine (DA) binds to DA receptors in the anterior pituitary and initiates a series of intracellular events culminating in the inhibition of prolactin release and synthesis. However, the biochemical mechanisms by which DA controls the secretion and synthesis of prolactin remain unknown. It has been suggested that the tonic level of prolactin release is maintained by influx of extracellular calcium and that DA inhibits this process (3-5). In addition, the role of intraceilular cyclic AMP is not yet well defined (5-10). The hydrolysis of phosphatidylinositol (PI) is thought to be an early event associated with the activation of receptors, which in turn act by producing changes in Ca ++ flux across the membrane (11,12). Generally, these receptors are not directly related to adenylate cyclase activity. (11). The increase in PI turnover may cause an increase of diglyceride (DG) and phosphatidic acid (PA), whicn have been shown to act as second messengers and ionophores (13,14). An increased turnover of PI has been shown to occur in the pituitary gland following the addition of various stimuli (15). Young _et_ _al. (16) showed that acetylcholine, which is able to stimulate the Ca++ efflux and the release of growth hormone from the anterior pituitary, also increases PI breakdown in the gland. More recently in GH3 clonal cells, the TRH-stimulated prolactin secretion has Deen related to a Ca++_dependent cell response and to an increased PI metabolism (17-19). The present study was designed to investigate the effect of DA and DA antagonists on the incorporation of 32p^ into PI and other phospnolipids by anterior pituitary glands in culture.