| 11029293 |
Pei JM, Yu XC, Fung ML, Zhou JJ, Cheung CS, Wong NS, Leung MP, Wong TM: Impaired G (s) alpha and adenylyl cyclase cause beta-adrenoceptor desensitization in chronically hypoxic rat hearts. Am J Physiol Cell Physiol. 2000 Nov;279(5):C1455-63.
The effects of beta-adrenoceptor stimulation with isoproterenol on electrically induced contraction and intracellular calcium ([Ca (2+)](i)) transient, and cAMP in myocytes from both hypertrophied right and nonhypertrophied left ventricles of rats exposed to 10% oxygen for 4 wk, were significantly attenuated. The increased [Ca (2+)](i) transient in response to cholera toxin was abolished, whereas increased cAMP after NaF significantly attenuated. The biologically active isoform, G (s) alpha-small (45 kDa), was reduced while the biologically inactive isoform, G (s) alpha-large (52 kDa), increased. The increased electrically induced [Ca (2+)](i) transient and cAMP with 10-100 microM forskolin were significantly attenuated in chronically hypoxic rats. The content of G (i) alpha (2), the predominant isoform of G (i) protein in the heart, was unchanged. Results indicate that impaired functions of G (s) protein and adenylyl cyclase cause beta-adrenoceptor desensitization. The impaired function of the G (s) protein may be due to reduced G (s) alpha-small and/or increased G (s) alpha-large, which does not result from changes in G (i) protein. Responses to all treatments were the same for right and left ventricles, indicating that the impaired cardiac functions are not secondary to cardiac hypertrophy. |
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