Schreiber G, Avissar S, Danon A, Belmaker R H
Beer Sheva Mental Health Centre, Ida and Solomon Stern Psychiatry Research Unit, Ben Gurion University, Israel.
Biol Psychiatry. 1991 Feb 1;29(3):273-80. doi: 10.1016/0006-3223(91)91289-4.
In a recent study, we found that lithium inhibits the function of guanine nucleotide-binding proteins, implicating G proteins as the common site for both the antimanic and antidepressant therapeutic effects of lithium. These findings may also suggest that an altered G protein function is of pathophysiological importance in bipolar affective disorder. In the present study, the coupling of both muscarinic-cholinergic receptors and beta-adrenergic receptors to pertussis toxin-sensitive G proteins or cholera toxin-sensitive G proteins was compared among untreated manic patients, lithium-treated euthymic bipolar patients, and healthy volunteers using mononuclear leukocyte (MNL) membrane preparations. Hyperactive function of G proteins was detected in untreated manic patients. Both isoproterenol-induced and carbamylcholine-induced increases in Gpp(NH)p binding capacity were twofold to threefold higher than the increases observed in healthy volunteers. On the other hand, lithium-treated euthymic bipolar patients showed G protein responses to agonist activation that were no different from the healthy volunteers. Altered G protein function may be of pathophysiological importance in bipolar affective disorder.
在最近的一项研究中，我们发现锂可抑制鸟嘌呤核苷酸结合蛋白的功能，这表明G蛋白是锂抗躁狂和抗抑郁治疗作用的共同位点。这些发现还可能提示，G蛋白功能改变在双相情感障碍中具有病理生理学重要性。在本研究中，使用单核白细胞（MNL）膜制剂，比较了未经治疗的躁狂患者、接受锂治疗的心境正常的双相患者和健康志愿者中，毒蕈碱胆碱能受体和β-肾上腺素能受体与百日咳毒素敏感的G蛋白或霍乱毒素敏感的G蛋白的偶联情况。在未经治疗的躁狂患者中检测到G蛋白功能亢进。异丙肾上腺素诱导和氨甲酰胆碱诱导的Gpp(NH)p结合能力增加比在健康志愿者中观察到的增加高两到三倍。另一方面，接受锂治疗的心境正常的双相患者对激动剂激活的G蛋白反应与健康志愿者无差异。G蛋白功能改变在双相情感障碍中可能具有病理生理学重要性。
