Coupling efficiencies of β₁- and β₂-adrenergic receptors expressed alone or together in transfected GH₃ pituitary cells

作     者：Guerrero, SW Minneman, KP 

作者机构：Emory Univ Dept Pharmacol Sch Med Atlanta GA 30322 USA 

出 版 物：《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》 (药理学与实验治疗学杂志)

年 卷 期：1999年第290卷第3期

页      面：980-988页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：NINDS NIH HHS [NS-21325] Funding Source: Medline 

主　　题：肾上腺素能β激动剂/代谢 肾上腺素能β激动剂/药理学 肾上腺素能β受体拮抗剂/代谢 肾上腺素能β受体拮抗剂/药理学 结合 竞争性 细胞 培养的 环AMP/代谢 咪唑类/代谢 咪唑类/药理学 碘放射性同位素 异丙硫半乳糖苷/药代动力学 异丙硫半乳糖苷/药理学 异丙肾上腺素/药理学 动力学 吲哚洛尔/类似物和衍生物 吲哚洛尔/代谢 吲哚洛尔/药理学 垂体 前叶/细胞学 垂体 前叶/代谢 垂体 前叶/生理学 丙醇胺类/代谢 丙醇胺类/药理学 受体 肾上腺素能β1/生物合成 受体 肾上腺素能β1/遗传学 受体 肾上腺素能β1/代谢 受体 肾上腺素能β2/生物合成 受体 肾上腺素能β2/遗传学 受体 肾上腺素能β2/代谢 转染 动物 大鼠 

摘      要：The relationship between rat beta(1)- and beta(2)-adrenergic receptors (ARs) and cyclic AMP (cAMP) responses was examined by inducible expression of each subtype in transfected GH, pituitary cells. Increasing expression of beta(1)- or beta(2)-ARs in stably transfected subclones increased basal cAMP, increased the potency of isoproterenol in stimulating cAMP formation, but did not change the maximal response. A linear relationship was observed between log B-max and -log EC50 for isoproterenol, with no significant differences between beta(1)- and beta(2)-ARs. When both subtypes were coexpressed at different densities and ratios, pharmacological analysis showed that both selective and nonselective agonists exerted their effects at least partially through both subtypes. Either subtype alone activated a maximal response when the other subtype was blocked, indicating a complete redundancy in coupling. Agonists could activate responses through either subtype, with responses mediated primarily through the subtype where the agonist was most potent. The nonselective agonist isoproterenol had similar potencies for activating both subtypes;however, the density and ratio of subtypes affected the relative potencies of the selective agonists norepinephrine and zinterol. We conclude that beta(1)- and beta(2)-ARs have similar coupling efficiencies in GH(3) cells, these efficiencies are not altered by coexpression of another subtype, they couple redundantly to cAMP formation, and the relative densities of beta(1)- and beta(2)-ARs control the potencies of selective agonists.