Tallent M, Reisine T
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104.
Mol Pharmacol. 1992 Mar;41(3):452-5.
Somatostatin (SRIF) receptors are coupled to the catalytic subunit of adenylyl cyclase via pertussis toxin-sensitive guanine nucleotide-binding regulatory proteins (G proteins). To identify which G proteins link SRIF receptors to adenylyl cyclase, G(o) alpha, Gi alpha, and its different subtypes were individually blocked in AtT-20 cell membranes with G alpha subtype-selective antisera. Antiserum directed against the carboxyl-terminal region of Gi alpha blocked SRIF inhibition of forskolin-stimulated adenylyl cyclase activity, and this effect was prevented by the peptide to which the antiserum was generated. However, antiserum directed against the carboxyl-terminal region of G(o) alpha did not affect SRIF inhibition of adenylyl cyclase activity, indicating that Gi alpha couples SRIF receptors to adenylyl cyclase but G(o) alpha does not. Peptide-directed antisera against Gi alpha 1 completely blocked SRIF inhibition of adenylyl cyclase activity. In contrast, antisera directed against either Gi alpha 2 or Gi alpha 3 did not affect the actions of SRIF. The results of these studies indicate that Gi alpha 1 selectively couples SRIF receptors to the catalytic subunit of adenylyl cyclase in AtT-20 cell membranes. Because previous studies have shown that SRIF receptors are able to couple to Gi alpha 1, Gi alpha 3, and G(o) alpha, the results suggest that different G proteins may specify the coupling of SRIF receptors to distinct cellular effector systems.
生长抑素（SRIF）受体通过百日咳毒素敏感的鸟嘌呤核苷酸结合调节蛋白（G蛋白）与腺苷酸环化酶的催化亚基偶联。为了确定哪些G蛋白将SRIF受体与腺苷酸环化酶相连，用Gα亚型选择性抗血清在AtT - 20细胞膜中分别阻断G(o)α、Giα及其不同亚型。针对Giα羧基末端区域的抗血清阻断了SRIF对福斯高林刺激的腺苷酸环化酶活性的抑制作用，并且该抗血清所针对的肽可阻止这种效应。然而，针对G(o)α羧基末端区域的抗血清并不影响SRIF对腺苷酸环化酶活性的抑制作用，这表明Giα将SRIF受体与腺苷酸环化酶偶联，而G(o)α则不然。针对Giα1的肽导向抗血清完全阻断了SRIF对腺苷酸环化酶活性的抑制作用。相比之下，针对Giα2或Giα3的抗血清并不影响SRIF的作用。这些研究结果表明，在AtT - 20细胞膜中，Giα1选择性地将SRIF受体与腺苷酸环化酶的催化亚基偶联。由于先前的研究表明SRIF受体能够与Giα1、Giα3和G(o)α偶联，因此结果表明不同的G蛋白可能决定SRIF受体与不同细胞效应系统的偶联。
