Reuter H, Porzig H
J Mol Cell Cardiol. 1985 Apr;17(4):307-16. doi: 10.1016/s0022-2828(85)80131-0.
Primary cultures of myocardial cells from neonatal rats were exposed for up to 5 days to the cyclic AMP derivative 8-Br-cAMP. After one day of exposure to the nucleotide, an increase in specific binding capacity of the hydrophilic beta-adrenoceptor antagonist 3H-CGP 12177 was observed in intact cells. (-)-Isoprenaline displaced the radioligand from its binding site. Neither the KD of the antagonist, nor that of the agonist were significantly affected by 8-Br-cAMP. The loss of beta-adrenoceptors during desensitization by long term treatment of the cells with isoprenaline could be partially prevented by 8-Br-cAMP. Only in desensitized, but not in normal cells was isoprenaline-induced cAMP formation significantly enhanced by 8-Br-cAMP pretreatment. This may indicate that beta-adrenoceptors which appear during 8-Br-cAMP exposure are poorly coupled to the adenylate cyclase. Alternatively, the change in receptor density may be accompanied by alterations of other components in the beta-adrenergic system, e.g. an inhibition of the adenylate cyclase. We suggest that cAMP-dependent feed-back regulation of the beta-adrenergic system may play a role during postnatal myocardial differentiation.
将新生大鼠的心肌细胞原代培养物暴露于环磷酸腺苷衍生物8-溴环磷酸腺苷（8-Br-cAMP）长达5天。在暴露于该核苷酸一天后，在完整细胞中观察到亲水性β-肾上腺素能拮抗剂3H-CGP 12177的特异性结合能力增加。（-）-异丙肾上腺素将放射性配体从其结合位点置换出来。拮抗剂的解离常数（KD）和激动剂的解离常数均未受到8-Br-cAMP的显著影响。用异丙肾上腺素长期处理细胞使其脱敏过程中β-肾上腺素能受体的丧失可被8-Br-cAMP部分阻止。只有在脱敏细胞中，而不是在正常细胞中，8-Br-cAMP预处理可显著增强异丙肾上腺素诱导的环磷酸腺苷（cAMP）形成。这可能表明在8-Br-cAMP暴露期间出现的β-肾上腺素能受体与腺苷酸环化酶的偶联较差。或者，受体密度的变化可能伴随着β-肾上腺素能系统中其他成分的改变，例如腺苷酸环化酶的抑制。我们认为β-肾上腺素能系统的环磷酸腺苷依赖性反馈调节可能在出生后心肌分化过程中起作用。
