Activation of type II adenylate cyclase by D2 and D4 but not D3 dopamine receptors

Val J. Watts, Kim A. Neve

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


The D2-like dopamine receptors couple to a variety of signal transduction pathways, including inhibition of adenylate cyclase, mitogenesis, and activation of potassium channels. Although these effects are mediated via pertussia toxin-sensitive G proteins, G(i/o) it is likely that some of these effects are influenced by the release of G protein βγ subunits. Type II adenylate cyclase (ACII) is highly regulated by multiple biochemical stimuli, including protein kinase C, forskolin, G protein α subunits, and G protein βγ subunits. The ability of βγ subunits to activate this enzyme in the presence of activated α(s) has been particularly well characterized. Although stimulation by βγ, subunits has been described as conditional on the presence of activated α(s) βγ subunits also potentiate ACII activity after activation of protein kinase C. We created stable cell lines expressing ACII and the D(2L) receptor, the D3 receptor, or the D4.4 receptor. Activation of D(2L) or D4.4 receptors, but not D3 receptors, potentiated β-adrenergic receptor/G(s)-stimulated activity of ACII, as measured by the intracellular accumulation of cAMP. Similarly, stimulation of D(2L) or D4.4 receptors potentiated phorbol ester- stimulated ACII activity in the absence of activated α(s), whereas stimulation of D3 receptors did not. The effect of D2-like receptor stimulation was blocked by pretreatment with pertussis toxin and by inhibition of protein kinase C. We propose that activation of both D(2L) and D4.4 dopamine receptors potentiated phorbol-12-myristate-13-acetate- stimulated ACII activity through the release of βγ subunits from pertussis toxin-sensitive G proteins. In contrast, the lack of D3 receptor-mediated effects suggests that stimulation of D3 receptors does not result in an appreciable release of βγ subunits.

Original languageEnglish (US)
Pages (from-to)181-186
Number of pages6
JournalMolecular pharmacology
Issue number2
StatePublished - Aug 1997

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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