GαL1 (Gα14) Couples the Opioid Receptor-Like1 Receptor to Stimulation of Phospholipase C

GαL1 (Gα14) Couples the Opioid Receptor-Like1 Receptor to Stimulation of Phospholipase C
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GαL1 (Gα14) 将阿片类受体样 1 受体与磷脂酶 C 的刺激结合

DOI:
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发表时间:
1999
期刊:
影响因子:
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通讯作者:
Y. Wong
Y. Wong
中科院分区:
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文献类型:
--
作者:
L. Yung;S. Joshi;R. Y. Chan;J. S. Chan;G. Pei;Y. Wong

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在大多数组织和细胞中,阿片受体样(ORL1)受体主要通过百日毒(PTX)敏感的鸟嘌呤核苷酸结合调节蛋白(G蛋白)Gi/Go来调节效应物。许多gi偶联受体具有与一种或多种ptx不敏感的G蛋白相互作用的额外能力。通过βγ诱导的2型腺苷酸环化酶的刺激,我们筛选了ORL1受体与一组ptx不敏感的G蛋白相互作用的能力。在PTX存在的情况下,ORL1受体的激活仅在共表达Gz、G12、G14或G16的α亚基的HEK 293细胞中导致2型腺苷酸环化酶的刺激,而在共表达G11、G13或Gq的细胞中则没有。由于已知ORL1受体的近亲阿片受体能与这些G蛋白有效偶联,因此预计会与Gz和G16偶联。ORL1受体与G12或G14的偶联尚未被证实。正如2型腺苷酸环化酶实验预测的那样,ORL1受体的激活导致g - α14瞬时共转染的COS-7细胞中肌醇磷酸的形成。orl1受体介导的磷脂酶C刺激是Gα14依赖性、激动剂剂量依赖性、配体选择性和PTX不敏感的。我们得出结论,G14可以将ORL1受体与磷脂酶C的调控联系起来。
In most tissues and cells the opioid receptor-like (ORL1) receptor regulates effectors primarily through the pertussis toxin (PTX)-sensitive guanine nucleotide-binding regulatory proteins (G proteins) Gi/Go. Many Gi-coupled receptors possess additional capability to interact with one or more PTX-insensitive G proteins. Using the βγ-induced stimulation of type 2 adenylyl cyclase as a readout, we screened the ability of ORL1 receptor to interact with a panel of PTX-insensitive G proteins. In the presence of PTX, activation of the ORL1 receptor resulted in the stimulation of type 2 adenylyl cyclase only in HEK 293 cells coexpressing the α subunit of Gz, G12, G14, or G16, but not in cells coexpressing G11, G13, or Gq. Coupling to both Gz and G16 was expected because close relatives of the ORL1 receptor, the opioid receptors, are known to couple productively to these G proteins. ORL1 receptor coupling to either G12 or G14 has not been demonstrated. As predicted by the type 2 adenylyl cyclase assays, activation of the ORL1 receptor resulted in the formation of inositol phosphates in COS-7 cells transiently cotransfected with Gα14. The ORL1receptor-mediated stimulation of phospholipase C was found to be Gα14 dependent, agonist dose dependent, ligand selective, and PTX insensitive. We conclude that G14 can link the ORL1 receptor to regulation of phopholipase C.
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