Recent evidences indicate the existence of an atypical D(1) dopamine receptor other than traditional D(1) dopamine receptor in the brain that mediates PI hydrolysis via activation of phospholipase C(beta) (PLC(beta)). To further understand the basic physiological function of this receptor in brain, the effects of a selective phosphoinositide (PI)-linked D(1) dopamine receptor agonist SKF83959 on cytosolic free calcium concentration ([Ca(2+)](i)) in cultured rat prefrontal cortical astrocytes were investigated by calcium imaging. The results indicated that SKF83959 caused a transient dose-dependent increase in [Ca(2+)](i). Application of D(1) receptor, but not D(2), alpha(1) adrenergic, 5-HT receptor, or cholinergic antagonist prevented SKF83959-induced [Ca(2+)](i) rise, indicating that activation of the D(1) dopamine receptor was essential for this response. Increase in [Ca(2+)](i) was a two-step process characterized by an initial increase in [Ca(2+)](i) mediated by release from intracellular stores, supplemented by influx through voltage-gated calcium channels, receptor-operated calcium channels, and capacitative Ca(2+) entry. Furthermore, SKF83959-stimulated increase in [Ca(2+)](i) was abolished following treatment with a PLC inhibitor. Overall, these results suggested that activation of D(1) receptor by SKF83959 mediates a dose-dependent mobilization of [Ca(2+)](i) via the PLC signaling pathway in cultured rat prefrontal cortical astrocytes.