Strassheim D, Palmer T, Milligan G, Houslay M D
Department of Biochemistry, University of Glasgow, Scotland, U.K.
Biochem J. 1991 May 15;276 ( Pt 1)(Pt 1):197-202. doi: 10.1042/bj2760197.
Attenuated maximal activations by forskolin, Mn+. NaF or guanosine 5'-[gamma-thio]triphosphate (GTP[S]) were noted for adenylate cyclase activity in adipocytes from obese (fa/fa) Zucker rats compared with their lean (Fa/Fa) littermates. GTP[S] achieved half-maximal activation of adenylate cyclase at some 10-fold lower concentrations in membranes from lean animals compared with those from obese. Levels of the 42 and 45 kDa forms of Gs were some 40-50% lower in membranes from obese animals, and levels of Gi-1 and Gi-3 were some 62-65% lower. No differences in levels of Gi-2 alpha-subunits or G-protein beta-subunits were observed. Gi function, as assessed by inhibiting forskolin-stimulated adenylate cyclase, achieved by prostaglandin E1, nicotinate and phenylisopropyladenosine, was similar in membranes from both lean and obese animals. Levels of beta-adrenoceptors were some 50% lower in membranes from obese animals. It is suggested that the attenuated activation of adenylate cyclase by stimulatory ligands in membranes from obese animals may be caused by decreases in both Gs and receptors, and that this may contribute to the attenuated lipolytic response seen in adipocytes from such animals.
与瘦的（Fa/Fa）同窝仔鼠相比，肥胖（fa/fa） Zucker大鼠脂肪细胞中，福斯可林、锰离子、氟化钠或鸟苷5'-[γ-硫代]三磷酸（GTP[S]）对腺苷酸环化酶活性的最大激活作用减弱。与肥胖动物的膜相比，在瘦动物的膜中，GTP[S]使腺苷酸环化酶达到半最大激活的浓度低约10倍。肥胖动物膜中42 kDa和45 kDa形式的Gs水平约低40 - 50%，Gi-1和Gi-3的水平约低62 - 65%。未观察到Gi-2α亚基或G蛋白β亚基水平的差异。通过前列腺素E1、烟酸酯和苯异丙基腺苷抑制福斯可林刺激的腺苷酸环化酶来评估的Gi功能，在瘦动物和肥胖动物的膜中相似。肥胖动物膜中β-肾上腺素能受体水平约低50%。提示肥胖动物膜中刺激配体对腺苷酸环化酶的激活减弱可能是由于Gs和受体均减少所致，这可能导致此类动物脂肪细胞中脂解反应减弱。
