Colucci W S
Circ Res. 1986 Feb;58(2):292-7. doi: 10.1161/01.res.58.2.292.
The purpose of this study was to determine whether a cyclic adenosine 3',5'-monophosphate-dependent process can be involved in the regulation of vascular smooth muscle alpha 1-adrenergic receptor responsiveness. Experiments were performed in cultured rabbit aortic smooth muscle cells which were characterized previously according to alpha-adrenergic receptor-binding characteristics and receptor-coupled norepinephrine-stimulated 45Ca++ efflux. The addition of dibutyryl-cyclic adenosine monophosphate to the cell culture medium for 24 hours resulted in a concentration-related decrease in maximal [3H]prazosin-binding capacity (41 +/- 4% decrease with 1 mM dibutyryl-cyclic adenosine monophosphate) without an effect on [3H]prazosin-binding affinity. Prostaglandin E1 (10 microM) and forskolin (10 microM) caused similar decreases in maximal [3H]prazosin-binding capacity, whereas butyrate (1 mM) and dibutyryl-guanosine-3',5' cyclic-monophosphate (1 mM) had no effect. Dibutyryl-cyclic adenosine monophosphate (1 mM) caused significant potentiation of the decrease in [3H]prazosin-binding caused by a submaximal (10 nM) but not a maximal (10 microM) concentration of norepinephrine, suggesting that cyclic adenosine monophosphate may act at a distal step in common with norepinephrine to reduce alpha-adrenergic receptor number. Despite the approximately 41% reduction in alpha-adrenergic receptor number following 24-hour incubation of cells with dibutyryl-cyclic adenosine monophosphate, maximal norepinephrine-stimulated 45Ca++ efflux was not reduced, consistent with the markedly nonlinear relationship between alpha-adrenergic receptor occupancy and maximal norepinephrine-stimulated 45Ca++ efflux in this cell system. These data provide evidence for a novel mechanism by which hormones or drugs which increase cyclic adenosine monophosphate levels can modulate alpha-adrenergic responsiveness in vascular smooth muscle.
本研究的目的是确定环磷酸腺苷（cAMP）依赖性过程是否参与血管平滑肌α1 - 肾上腺素能受体反应性的调节。实验在培养的兔主动脉平滑肌细胞中进行，这些细胞先前已根据α - 肾上腺素能受体结合特性和受体偶联的去甲肾上腺素刺激的45Ca++外流进行了表征。向细胞培养基中添加二丁酰环磷酸腺苷24小时导致最大[3H]哌唑嗪结合能力呈浓度依赖性降低（1 mM二丁酰环磷酸腺苷导致降低41±4%），而对[3H]哌唑嗪结合亲和力无影响。前列腺素E1（10 μM）和福斯可林（10 μM）导致最大[3H]哌唑嗪结合能力出现类似降低，而丁酸盐（1 mM）和二丁酰鸟苷 - 3',5' - 环磷酸（1 mM）则无作用。1 mM二丁酰环磷酸腺苷使由次最大浓度（10 nM）而非最大浓度（10 μM）的去甲肾上腺素引起的[3H]哌唑嗪结合降低得到显著增强，这表明环磷酸腺苷可能在与去甲肾上腺素共同的远端步骤起作用以减少α - 肾上腺素能受体数量。尽管用二丁酰环磷酸腺苷孵育细胞24小时后α - 肾上腺素能受体数量减少了约41%，但最大去甲肾上腺素刺激的45Ca++外流并未降低，这与该细胞系统中α - 肾上腺素能受体占有率与最大去甲肾上腺素刺激的45Ca++外流之间明显的非线性关系一致。这些数据为一种新机制提供了证据，即增加环磷酸腺苷水平的激素或药物可调节血管平滑肌中的α - 肾上腺素能反应性。
