D5 dopamine receptors are required for dopaminergic activation of phospholipase C

Mol Pharmacol. 2009 Mar;75(3):447-53. doi: 10.1124/mol.108.053017. Epub 2008 Dec 1.

Abstract

Dopamine activates phospholipase C in discrete regions of the mammalian brain, and this action is believed to be mediated through a D(1)-like receptor. Although multiple lines of evidence exclude a role for the D(1) subtype of D(1)-like receptors in the phosphoinositide response, the D(5) subtype has not been similarly examined. Here, mice lacking D(5) 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 D(5) receptor knockout mice significantly or completely lost the ability to produce inositol phosphate or diacylglycerol messengers after stimulation with dopamine or several selective D(1)-like receptor agonists. Moreover, endogenous inositol-1,4,5-trisphosphate stimulation by the phospholipase C-selective D(1)-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 D(5) receptor mutants. Hence, D(5) receptors are required for dopamine and selective D(1)-like agonists to induce phospholipase C-mediated phosphoinositide signaling in the mammalian brain.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Dopamine Agonists / pharmacology*
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Dopamine D5 / agonists*
  • Receptors, Dopamine D5 / deficiency
  • Receptors, Dopamine D5 / physiology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Type C Phospholipases / metabolism*

Substances

  • Dopamine Agonists
  • Receptors, Dopamine D5
  • Type C Phospholipases