Akhter S A, Luttrell L M, Rockman H A, Iaccarino G, Lefkowitz R J, Koch W J
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Science. 1998 Apr 24;280(5363):574-7. doi: 10.1126/science.280.5363.574.
Hormones and neurotransmitters may mediate common responses through receptors that couple to the same class of heterotrimeric guanine nucleotide-binding (G) protein. For example, several receptors that couple to Gq class proteins can induce cardiomyocyte hypertrophy. Class-specific inhibition of Gq-mediated signaling was produced in the hearts of transgenic mice by targeted expression of a carboxyl-terminal peptide of the alpha subunit Galphaq. When pressure overload was surgically induced, the transgenic mice developed significantly less ventricular hypertrophy than control animals. The data demonstrate the role of myocardial Gq in the initiation of myocardial hypertrophy and indicate a possible strategy for preventing pathophysiological signaling by simultaneously blocking multiple receptors coupled to Gq.
激素和神经递质可能通过与同一类异源三聚体鸟嘌呤核苷酸结合（G）蛋白偶联的受体介导共同反应。例如，几种与Gq类蛋白偶联的受体可诱导心肌细胞肥大。通过靶向表达α亚基Gαq的羧基末端肽，在转基因小鼠心脏中产生了对Gq介导信号传导的类别特异性抑制。当通过手术诱导压力超负荷时，转基因小鼠发生的心室肥大明显少于对照动物。这些数据证明了心肌Gq在心肌肥大起始中的作用，并表明了一种通过同时阻断多个与Gq偶联的受体来预防病理生理信号传导的可能策略。
