ACCELERATED COMMUNICATION D5 Dopamine Receptors are Required for Dopaminergic Activation of Phospholipase C

Dopamine activates phospholipase C in discrete regions of the mammalian brain, and this action is believed to be mediated through a D1-like receptor. Although multiple lines of evidence exclude a role for the D1 subtype of D1-like receptors in the phosphoinositide response, the D5 subtype has not been sim-ilarly examined. Here, mice lacking D5 dopamine receptors were tested for dopamine agonist-induced phosphoinositide signaling both in vitro and in vivo. The results show that hip-pocampal, cortical, and striatal tissues of D5 receptor knockout mice significantly or completely lost the ability to produce ino-sitol phosphate or diacylglycerol messengers after stimulation with dopamine or several selective D1-like receptor agonists. Moreover, endogenous inositol-1,4,5-trisphosphate stimulation by the phospholipase C-selective D1-like agonist 3-methyl-6