The beta2-adrenergic receptor specifically sequesters Gs but signals through both Gs and Gi/o in rat sympathetic neurons.
The beta2-adrenergic receptor specifically sequesters Gs but signals through both Gs and Gi/o in rat sympathetic neurons.
复制标题
β2-肾上腺素能受体特异性地隔离 Gs，但在大鼠交感神经元中通过 Gs 和 Gi/o 发出信号。
DOI：
10.1016/s0306-4522(03)00024-1
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发表时间：
2003
期刊：
影响因子：
3.3
通讯作者：
Lewis,DL
中科院分区：
文献类型：
--
作者：
Vásquez,C;Lewis,DL
β2-肾上腺素能受体（β2-AR）和CB 1大麻素受体具有组成性活性的特性。CB 1大麻素受体也可以隔离Gi/o蛋白;然而，尚不清楚β2-AR是否也可以隔离G蛋白。用显微注射法和膜片钳技术研究了β2-AR在大鼠上级颈神经节神经元中的异源表达。β-AR激动剂异丙肾上腺素使注射100 ng/μl β2-AR cDNA的神经元钙电流增加25.9±1.6%，而对对照神经元无影响。用霍乱毒素（CTX）预处理可消除异丙肾上腺素的作用，表明通过G蛋白偶联。在注射200 ng/μl β2-AR cDNA的神经元中，异丙肾上腺素则相反，对Ca ~（2+）电流的抑制率为36.5± 2.0%。Ca ~（2+）电流的抑制对百日咳毒素敏感，表明β2-AR与Gi/o蛋白偶联。用CTX预处理导致更大的54±3.8%的Ca 2+电流抑制，表明Gscoupling掩盖了Gi/ocoupling的全部作用。β2-AR的表达可阻断血管活性肠肽（VIP）的Gs偶联受体信号传导。VIP对对照神经元钙电流的抑制率为49.5±0.5%，而对β2-AR表达神经元无明显影响。相反，β2-AR的表达对Gi/o偶联α2-肾上腺素能受体的信号传导没有影响。本研究表明，β2-AR与G蛋白和G蛋白偶联，但特异性地螯合G蛋白，阻止它们与另一个G蛋白偶联受体相互作用。因此，β2-肾上腺素能受体具有阻止其他GS偶联受体转导其生物信号的潜力。
β2-adrenergic receptors (β2-AR) and CB1 cannabinoid receptors share the property of being constitutively active. The CB1 cannabinoid receptor can also sequester Gi/oproteins; however, it is not known whether the β2-AR can also sequester G proteins. β2-ARs were heterologously expressed in rat superior cervical ganglion neurons by microinjection of cDNA and studied using the patch-clamp technique. The β-AR agonist isoproterenol increased the Ca2+current 25.9±1.6% in neurons microinjected with 100 ng/μl β2-AR cDNA but was without effect on control neurons. Pretreatment with cholera toxin (CTX) abolished the effect of isoproterenol, indicating coupling via Gsproteins. In neurons microinjected with 200 ng/μl β2-AR cDNA, isoproterenol had the opposite effect of inhibiting the Ca2+current 36.5±2.0%. Inhibition of the Ca2+current was sensitive to pertussis toxin, indicating β2-AR coupling to Gi/oproteins. Pretreatment with CTX resulted in a greater 54±3.8% inhibition of the Ca2+current, indicating that Gscoupling masks the full effect of Gi/ocoupling. Expression of β2-ARs abolished signaling by Gs-coupled receptors for vasoactive intestinal polypeptide (VIP). VIP inhibited the Ca2+current 49.5±0.5% in control neurons but had no effect in neurons expressing β2-ARs. In contrast, expression of β2-ARs had no effect on signaling by the Gi/o-coupled α2-adrenergic receptor. This study demonstrates that the β2-AR couples to both Gsand Gi/oproteins but specifically sequesters Gsproteins, preventing their interaction with another Gs-coupled receptor. β2-adrenergic receptors thus have the potential to prevent other Gs-coupled receptors from transducing their biological signals.