| 8989144 |
Li HT, Honbo NY, Karliner JS: Chronic hypoxia increases beta 1-adrenergic receptor mRNA and density but not signaling in neonatal rat cardiac myocytes. Circulation. 1996 Dec 15;94(12):3303-10.
BACKGROUND: It is well recognized that the beta-adrenergic receptor-adenylylcyclase system is altered during myocardial ischemia/hypoxia. However, there are no data regarding either regulation of beta-adrenergic receptors, particularly at the mRNA level, or adenylylcyclase activity in isolated cardiac myocytes exposed to chronic hypoxia. METHODS AND RESULTS: In a chronic hypoxia model in which neonatal rat ventricular myocytes were exposed to a 1% O2 environment for 72 hours, we investigated (1) beta 1-mRNA and receptor expression and adenylylcyclase activity and (2) beta 1-mRNA and receptor downregulation and adenylylcyclase desensitization induced by prolonged norepinephrine incubation. We found that hypoxia for 72 hours increased myocardial membrane beta 1-adrenergic receptor density by 44%. This increase was not associated with a corresponding decrease in cytosolic beta 1-adrenergic receptors. RNase protection assays demonstrated that hypoxia increased the steady-state levels of beta 1-mRNA by 109%. Adenylylcyclase activity stimulated by isoproterenol, sodium fluoride, guanyl-5'-imidodiphosphate, and forskolin in hypoxic membranes was not altered compared with normoxic controls. Hypoxia for 72 hours also did not affect norepinephrine-induced beta 1-mRNA and receptor downregulation and adenylylcyclase desensitization in response to isoproterenol, guanyl-5'-imidodiphosphate, or forskolin. CONCLUSIONS: In neonatal rat cardiac myocytes, chronic hypoxia (1) increases beta 1-mRNA and receptor expression but does not alter adenylylcyclase activity stimulated at either the receptor or the postreceptor level and (2) does not affect agonist-induced beta 1-mRNA and receptor downregulation and desensitization of the adenylylcyclase response. |
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