Department of Biomedical & Diagnostic Science, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN, United States.
Vitam Horm. 2019;111:299-311. doi: 10.1016/bs.vh.2019.05.009. Epub 2019 Jun 21.
The development, progression, metastasis and drug resistance of the most common human cancers are driven by cyclic adenosine monophosphate (cAMP)-signaling downstream of beta-adrenergic receptors (β-Ars) coupled to the stimulatory G-protein G. Receptors coupled to the inhibitory G-protein G inhibit this signaling cascade by blocking the activation of the enzyme adenylyl cyclase that catalyzes the formation of cAMP and function as the physiological inhibitors of this signaling cascade. Members of the G-coupled receptor family widely expressed in the mammalian organism are GABA B receptors (GABA-Rs) for the inhibitory neurotransmitter γ-aminobutyric acid (GABA), opioid receptors for endogenous opioid peptides and cannabinoid receptors for endogenous cannabinoids. This review summarizes current evidence for the concept that the activation of G-receptor signaling by pharmacological and psychological means is a promising tool for the long-term management of cAMP-driven cancers with special emphasis on the inhibitory effects of opioids on lung adenocarcinoma and its stem cells.
最常见的人类癌症的发展、进展、转移和耐药性是由β肾上腺素能受体（β-Ars）下游的环腺苷酸单磷酸（cAMP）信号驱动的，β-Ars 与刺激 G 蛋白 G 偶联。与抑制 G 蛋白 G 偶联的受体通过阻断催化 cAMP 形成的酶腺苷酸环化酶的激活来抑制这种信号级联，并且作为该信号级联的生理抑制剂起作用。在哺乳动物中广泛表达的 G 偶联受体家族的成员是 GABA B 受体（GABA-Rs），用于抑制性神经递质 γ-氨基丁酸（GABA），内源性阿片肽的阿片受体和内源性大麻素的大麻素受体。这篇综述总结了目前的证据，即通过药理学和心理学手段激活 G 受体信号是长期管理 cAMP 驱动的癌症的有前途的工具，特别强调了阿片类药物对肺腺癌及其干细胞的抑制作用。
