Guerrero S W, Zhong H, Minneman K P
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Receptor. 1995;5(4):185-95.
We studied the effects of changing beta 1- and beta 2-adrenergic receptor (AR) subtype ratios and densities on cyclic AMP (cAMP) responses to norepinephrine (NE) and epinephrine (EPI) in rat C6 glioma cells. Dexamethasone (DEX) increased beta 2- and decreased beta 1-AR expression without changing total beta-AR density, whereas pretreatment with selective agonists specifically downregulated each subtype. Combinations of these treatments produced cells with six different beta 2/beta 1 ratios that ranged from 0 (100% beta 1) to 2.85. We compared the effects of NE and EPI on cAMP accumulation in each condition and observed a predominantly beta 1 pharmacology (NE > EPI) under most conditions. However, as the beta 2-AR density exceeded the number of beta 1-ARs we observed a progressive shift toward a more beta 2-like pharmacology (EPI > NE), without the appearance of biphasic concentration-response curves. The ratio of beta 2/beta 1 density correlated significantly (p < 0.006) with the ratio of the potencies of NE and EPI in increasing cAMP formation. We conclude that in native C6 cells beta 1-ARs appear to couple more efficiently to cAMP accumulation than do beta 2-ARs, but both subtypes contribute to catecholamine responses in a nonadditive manner when the proportion of beta 2-ARs is increased.
我们研究了改变β1-和β2-肾上腺素能受体（AR）亚型比例及密度对大鼠C6胶质瘤细胞中环磷酸腺苷（cAMP）对去甲肾上腺素（NE）和肾上腺素（EPI）反应的影响。地塞米松（DEX）增加β2-AR表达并降低β1-AR表达，而不改变总β-AR密度，而用选择性激动剂预处理可特异性下调各亚型。这些处理的组合产生了六种不同β2/β1比例的细胞，范围从0（100%β1）到2.85。我们比较了NE和EPI在每种条件下对cAMP积累的影响，发现在大多数条件下主要呈现β1药理学特征（NE>EPI）。然而，当β2-AR密度超过β1-AR数量时，我们观察到逐渐向更类似β2的药理学特征转变（EPI>NE），且未出现双相浓度-反应曲线。β2/β1密度比值与NE和EPI增加cAMP生成的效能比值显著相关（p<0.006）。我们得出结论，在天然C6细胞中，β1-ARs似乎比β2-ARs更有效地与cAMP积累偶联，但当β2-ARs比例增加时，两种亚型以非加性方式对儿茶酚胺反应起作用。
