Dopamine D2L receptor couples to Gαi2 and Gαi3 but not Gαi1, leading to the inhibition of adenylate cyclase in transfected cell lines

C. M. O'Hara, L. Tang, R. Taussig, R. D. Todd, K. L. O'Malley

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Abstract

Previously, we showed that both D2 and D4 dopamine receptors inhibited adenylate cyclase in a pertussis toxin (Ptx)-sensitive manner in the dopamine-producing MN9D cell line, whereas only D2 receptors did so in a fibroblast cell line, CCL1.3. Of the known Ptx-sensitive G proteins, MN9D cells expressed Gαi2, GαoA and GαoB, whereas CCL1.3 cells expressed only Gαi2. Here we cotransfected MN9D and CCL1.3 cells with either the long form of the D2 receptor (D2L) or the D4 receptor and a mutant Ptx-resistant G protein α-subunit. When cotransfected CCL1.3 cell lines were tested for the ability of Ptx to block receptor-mediated inhibition of cyclic AMP accumulation, D2 receptors were found to couple to mutant Gαi2 and Gαi3 but not Gαi1 or GαoA. D2 also coupled to mutant Gα12 but not GαoA in MN9D cells. In contrast, D4 receptors did not couple to either mutant Gαi2 or GαoA subunits in MN9D cells. These data suggest that D4 receptor-mediated inhibition of adenylate cyclase is not coupled via the same mechanisms used by D2 receptors. D2L receptors are capable of coupling to more than one G protein in the modulation of cyclic AMP.

Original languageEnglish (US)
Pages (from-to)354-360
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume278
Issue number1
StatePublished - Jul 1 1996

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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