Yu J L, Hui K K
Department of Medicine, UCLA School of Medicine 90024.
Res Commun Chem Pathol Pharmacol. 1988 Jul;61(1):3-16.
The effects of forskolin on L-isoproterenol induced beta adrenoceptor desensitization in intact human lymphocytes from healthy subjects were studied. Exposure of intact lymphocytes to 50 microM L-isoproterenol for 150 minutes at 37 degrees C induced a 18% loss in beta adrenergic receptor density (Bmax) as characterized by using [3H]-DHA at 25 degrees C (23% loss, at 4 degrees C) as well as a significant loss in cyclic AMP responsiveness of the cell to isoproterenol restimulation. The addition of 10 microM forskolin to 50 microM isoproterenol potentiated isoproterenol induced beta 2 adrenoceptor desensitization as shown by further reduction in [3H]-DHA binding sites (decreased by 40% at 25 degrees C, 45% at 4 degrees C) and corresponding decrease in cyclic AMP responsiveness. These suggest that isoproterenol and forskolin act in a cooperative manner not only in the activation of adenylate cyclase and cyclic AMP generation but also in the regulation of hormone receptor and adenylate cyclase coupling.
研究了福斯高林对健康受试者完整人淋巴细胞中L-异丙肾上腺素诱导的β肾上腺素能受体脱敏的影响。在37℃下，将完整淋巴细胞暴露于50μM L-异丙肾上腺素150分钟，可导致β肾上腺素能受体密度（Bmax）降低18%，这是通过在25℃下使用[3H]-DHA进行表征的（在4℃下降低23%），同时细胞对异丙肾上腺素再刺激的环磷酸腺苷反应性也显著降低。向50μM异丙肾上腺素中添加10μM福斯高林可增强异丙肾上腺素诱导的β2肾上腺素能受体脱敏，这表现为[3H]-DHA结合位点进一步减少（在25℃下减少40%，在4℃下减少45%）以及环磷酸腺苷反应性相应降低。这些表明异丙肾上腺素和福斯高林不仅在激活腺苷酸环化酶和生成环磷酸腺苷方面协同作用，而且在调节激素受体和腺苷酸环化酶偶联方面也协同作用。
