DOPAMINE D-2L RECEPTOR COUPLES TO G-ALPHA(I2) AND G-ALPHA(I3) BUT NOTG-ALPHA(I1), LEADING TO THE INHIBITION OF ADENYLATE-CYCLASE IN TRANSFECTED CELL-LINES

Previously, we showed that both D-2, and D-4 dopamine receptors inhibi ted adenylate cyclase in a pertussis toxin (Ptx)-sensitive manner in t he dopamine-producing MN9D cell line, whereas only D-2 receptors did s o in a fibroblast cell line CCL1.3. Of the known Ptx-sensitive G prote ins, MN9D cells expressed G alpha(i2), G alpha(oA), and G alpha(oB), w hereas CCL1.3 cells, expressed only G alpha(i2). Here we cotransfected MN9D and CCL1.3 cells with either the long form of the D-2 receptor ( D-2L) or the D-4 receptor and a mutant Ptx-resistant G protein alpha-s ubunit. When cotransfected CCL1.3 cell lines were tested for the abili ty of Ptx to block receptor-mediated inhibition of cyclic AMP accumula tion, D-2 receptors were found to couple to mutant G alpha(i2) and G a lpha(i3) but not G alpha(i1) or G alpha(oA). D-2 also coupled to mutan t G alpha(i2) but not G alpha(oA) in MN9D cells. In contrast, D-4 rece ptors did not couple to either mutant G alpha(i2) or G alpha(oA) subun its in MN9D cells. These data suggest that D-4 receptor-mediated inhib ition of adenylate cyclase is not coupled via the same mechanisms used by D-2 receptors. D-2L receptors are capable of coupling to more than one G protein in the modulation of cyclic AMP.