TARGETING THE RECEPTOR-G(Q) INTERFACE TO INHIBIT IN-VIVO PRESSURE-OVERLOAD MYOCARDIAL HYPERTROPHY

Hormones and neurotransmitters may mediate common responses through re ceptors that couple to the same class of heterotrimeric guanine nucleo tide-binding (G) protein. For example, several receptors that couple t o G(q) class proteins can induce cardiomyocyte hypertrophy. Class-spec ific inhibition of G(q)-mediated signaling was produced in the hearts of transgenic mice by targeted expression of a carboxyl-terminal pepti de of the alpha subunit G alpha(q). When pressure overload was surgica lly induced, the transgenic mice developed significantly less ventricu lar hypertrophy than control animals. The data demonstrate the role of myocardial G(q) in the initiation of myocardial hypertrophy and indic ate a possible strategy for preventing pathophysiological signaling by simultaneously blocking multiple receptors coupled to G(q).