Dopamine D2L receptor couples to G alpha i2 and G alpha i3 but not G alpha i1, leading to the inhibition of adenylate cyclase in transfected cell lines.
Dopamine D2L receptor couples to G alpha i2 and G alpha i3 but not G alpha i1, leading to the inhibition of adenylate cyclase in transfected cell lines.
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发表时间：
1996-07
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通讯作者：
C. O'Hara;L. Tang;R. Taussig;R. Todd;K. O’Malley
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作者：
C. O'Hara;L. Tang;R. Taussig;R. Todd;K. O’Malley
此前，我们发现，在产生多巴胺的 MN9D 细胞系中，D2 和 D4 多巴胺受体均以百日咳毒素 (Ptx) 敏感的方式抑制腺苷酸环化酶，而在成纤维细胞系 CCL1.3 中，只有 D2 受体能抑制腺苷酸环化酶。在已知的 Ptx 敏感 G 蛋白中，MN9D 细胞表达 G α i2、G α oA 和 G α oB，而 CCL1.3 细胞仅表达 G α i2。在这里，我们用长形式的 D2 受体 (D2L) 或 D4 受体以及突变型 Ptx 抗性 G 蛋白 α 亚基共转染 MN9D 和 CCL1.3 细胞。当测试共转染的 CCL1.3 细胞系的 Ptx 阻断受体介导的环 AMP 积累抑制的能力时，发现 D2 受体与突变型 G α i2 和 G α i3 偶联，但不与 G α i1 或 G α oA 偶联。 D2 还与 MN9D 细胞中的突变型 G α i2 偶联，但不与 G α oA 偶联。相反，D4 受体不与 MN9D 细胞中的突变 G α i2 或 G α oA 亚基偶联。这些数据表明，D4 受体介导的腺苷酸环化酶抑制并非通过 D2 受体使用的相同机制耦合。 D2L 受体能够与不止一种 G 蛋白偶联来调节环 AMP。
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 G alpha i2, G alpha oA and G alpha oB, whereas CCL1.3 cells expressed only G alpha i2. 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 alpha-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 G alpha i2 and G alpha i3 but not G alpha i1 or G alpha oA. D2 also coupled to mutant G alpha i2 but not G alpha oA in MN9D cells. In contrast, D4 receptors did not couple to either mutant G alpha i2 or G alpha 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. D2L receptors are capable of coupling to more than one G protein in the modulation of cyclic AMP.