Dopamine D(2L) receptor couples to gα(i2) and gα(i3) but not gα(i1), 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 Gα(i2), Gα(oA) and Gα(oB), whereas COL1.3 cells expressed only Gα(i2). Here we cotransfected MN9D and CCL1.3 cells with either the long form of the D2 receptor (D(2L)) 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 Gα(i2) and Gα(i3) but not Gα(i1) or Gα(oA). D2 also coupled to mutant Gα(i2) but not Gα(oA) in MN9D cells. In contrast, D4 receptors did not couple to either mutant Gα(i2) or Gα(oA) 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. D(2L) 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 - 1996

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Pertussis Toxin
Adenylyl Cyclases
Dopamine
GTP-Binding Proteins
Cell Line
Cyclic AMP
Dopamine D4 Receptors
Gastrin-Secreting Cells
Dopamine D2 Receptors
Protein Subunits
Fibroblasts

ASJC Scopus subject areas

  • Pharmacology

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Dopamine D(2L) receptor couples to gα(i2) and gα(i3) but not gα(i1), leading to the inhibition of adenylate cyclase in transfected cell lines. / O'Hara, C. M.; Tang, L.; Taussig, R.; Todd, R. D.; O'Malley, K. L.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 278, No. 1, 1996, p. 354-360.

Research output: Contribution to journalArticle

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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 Gα(i2), Gα(oA) and Gα(oB), whereas COL1.3 cells expressed only Gα(i2). Here we cotransfected MN9D and CCL1.3 cells with either the long form of the D2 receptor (D(2L)) 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 Gα(i2) and Gα(i3) but not Gα(i1) or Gα(oA). D2 also coupled to mutant Gα(i2) but not Gα(oA) in MN9D cells. In contrast, D4 receptors did not couple to either mutant Gα(i2) or Gα(oA) 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. D(2L) receptors are capable of coupling to more than one G protein in the modulation of cyclic AMP.",
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