Dopamine D2 receptors attenuate phosphatidylinositol 4,5-bisphosphate in synaptosomal membranes from rat neostriatum.

The effects of dopamine on [32P]ATP-labelled phosphatidylinositol 4-phosphate, phosphatidylinositol 4,5-bisphosphate, and phosphatidic acid were analyzed by TLC in synaptosomal membranes of the rat neostriatum. The incorporation of 32P into these compounds was found to be stable within 1 min and was maintained during the 30 min of incubation. Dopamine (0.1-10 microM) was found to attenuate the levels of phosphatidylinositol 4,5-bisphosphate without affecting the levels of phosphatidylinositol 4-phosphate or phosphatidic acid. The maximal decrease (-35 +/- 4%) was reached at 10 microM of dopamine after 30 min of incubation. The dopamine (0.1 microM)-induced decrease was blocked by the D2 selective antagonist raclopride (1 microM), but not by the D1 selective antagonist SCH 23390 (1 microM). These findings indicate the existence of an intramembrane coupling of dopamine D2 receptors to phosphoinositide turnover and may underlie some of the physiological effects of D2 receptor stimulation.