D5 Dopamine Receptors are Required for Dopaminergic Activation of Phospholipase C

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Abstract
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 similarly 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 hippocampal, cortical, and striatal tissues of D5 receptor knockout mice significantly or completely lost the ability to produce inositol 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-chloro-7,8-dihydroxy-1-[3methylphenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) was robust in wild-type animals but undetectable in the D5 receptor mutants. Hence, D5 receptors are required for dopamine and selective D1-like agonists to induce phospholipase C-mediated phosphoinositide signaling in the mammalian brain.

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