Impaired G(s)alpha and adenylyl cyclase cause beta-adrenoceptor desensitization in chronically hypoxic rat hearts |
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Authors: | Pei J M Yu X C Fung M L Zhou J J Cheung C S Wong N S Leung M P Wong T M |
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Institution: | Department of Physiology, Faculty of Medicine, University of Hong Kong, Hong Kong, China. |
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Abstract: | The effectsof -adrenoceptor stimulation with isoproterenol on electricallyinduced contraction and intracellular calcium (Ca2+]i) transient, and cAMP inmyocytes from both hypertrophied right and nonhypertrophied leftventricles of rats exposed to 10% oxygen for 4 wk, were significantlyattenuated. The increased Ca2+]i transientin response to cholera toxin was abolished, whereas increased cAMPafter NaF significantly attenuated. The biologically activeisoform, Gs -small (45 kDa), was reduced while thebiologically inactive isoform, Gs -large (52 kDa),increased. The increased electrically inducedCa2+]i transient and cAMP with 10-100µM forskolin were significantly attenuated in chronically hypoxicrats. The content of Gi 2, the predominantisoform of Gi protein in the heart, was unchanged. Resultsindicate that impaired functions of Gs protein and adenylyl cyclase cause -adrenoceptor desensitization. The impaired function of the Gs protein may be due to reducedGs -small and/or increased Gs -large, whichdoes not result from changes in Gi protein. Responses toall treatments were the same for right and left ventricles, indicatingthat the impaired cardiac functions are not secondary to cardiac hypertrophy. |
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