Targeting the receptor-G(q) interface to inhibit in vivo pressure overload myocardial hypertrophy

Shahab A. Akhter, Louis M. Luttrell, Howard A. Rockman, Guido Iaccarino, Robert J. Lefkowitz, Walter J. Koch

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Abstract

Hormones ad neurotransmitters may mediate common responses through receptors that couple to the same class of heterotrimerio guanine nucleotide- binding (G) protein. For example, several receptors that couple to G(q) class proteins can induce cardiomyocyte hypertrophy. Class-specific inhibition of G(q) mediated signaling was produced in the hearts of transgenic mice by targeted expression of a carboxyl-terminal peptide of the α subunit Gα(q). When pressure overload was surgically induced, the transgenic mice developed significantly less ventricular hypertrophy than control animals. The data demonstrate the role of myocardial G(q) in the initiation of myocardial hypertrophy and indicate a possible strategy for preventing pathophysiological signaling by simultaneously blocking multiple receptors coupled to G(q).

Original languageEnglish
Pages (from-to)574-577
Number of pages4
JournalScience
Volume280
Issue number5363
DOIs
Publication statusPublished - Apr 24 1998

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Cite this

Akhter, S. A., Luttrell, L. M., Rockman, H. A., Iaccarino, G., Lefkowitz, R. J., & Koch, W. J. (1998). Targeting the receptor-G(q) interface to inhibit in vivo pressure overload myocardial hypertrophy. Science, 280(5363), 574-577. https://doi.org/10.1126/science.280.5363.574