Modulation of Ca 2+ signals by phosphatidylinositol‐linked novel D1 dopamine receptor in hippocampal neurons

Recent evidence indicates the existence of a putative novel phosphatidylinositol‐linked D1 dopamine receptor in brain that mediates phosphatidylinositol hydrolysis via activation of phospholipase Cβ. The present work was designed to characterize the Ca 2+ signals regulated by this phosphatidylinositol‐linked D 1 dopamine receptor in primary cultures of hippocampal neurons. The results indicated that stimulation of phosphatidylinositol‐linked D1 dopamine receptor by its newly identified selective agonist SKF83959 induced a long‐lasting increase in basal [Ca 2+ ] i in a time‐ and dose‐dependent manner. Stimulation was observable at 0.1 μ m and reached the maximal effect at 30 μ m . The [Ca 2+ ] i increase induced by 1 μ m SKF83959 reached a plateau in 5 ± 2.13 min, an average 96 ± 5.6% increase over control. The sustained elevation of [Ca 2+ ] i was due to both intracellular calcium release and calcium influx. The initial component of Ca 2+ increase through release from intracellular stores was necessary for triggering the late component of Ca 2+ rise through influx. We further demonstrated that activation of phospholipase Cβ/inositol triphosphate was responsible for SKF83959‐induced Ca 2+ release from intracellular stores. Moreover, inhibition of voltage‐operated calcium channel or NMDA receptor‐gated calcium channel strongly attenuated SKF83959‐induced Ca 2+ influx, indicating that both voltage‐operated calcium channel and NMDA receptor contribute to phosphatidylinositol‐linked D 1 receptor regulation of [Ca 2+ ] i .