首页   按字顺浏览 期刊浏览 卷期浏览 Inactivation of the β-adrenergic receptor in cardiac muscle by dithiols
Inactivation of the β-adrenergic receptor in cardiac muscle by dithiols

 

作者: Trevor I. Prior,   Vandana Patel,   G. I. Drummond,  

 

期刊: Canadian Journal of Physiology and Pharmacology  (NRC Available online 1985)
卷期: Volume 63, issue 8  

页码: 932-936

 

ISSN:0008-4212

 

年代: 1985

 

DOI:10.1139/y85-154

 

出版商: NRC Research Press

 

数据来源: NRC

 

摘要:

The effect of sulfhydryl reagents on binding of the β-adrenergic antagonist (−)-[3H]dihydroalprenolol hydrochloride ((−)-[3H]DHA) to a microsomal fraction of rabbit ventricular muscle was studied. Incubation with the disulfide reducing agents dithiothreitol (DTT), 2-mercaptocthanol, and reduced glutathione resulted in loss of (−)-[3H]DHA binding. At 500 μMDTT, less than 50% of specific binding activity remained; at 100 mM, binding was completely eliminated. 2-Mercaptoethanol and reduced glutathione were less effective than DTT at inhibiting binding activity. The total binding capacity (Bmax) decreased from 155.4 fmol mg−1of protein, in the absence of DTT, to 92.4 and 77.5 fmol mg−1at 0.25 and 0.7 mMDTT, respectively. The equilibrium dissociation constant (KD) increased from 7.6 nM, in the absence of DTT, to 10.3 nMat 0.25 mMDTT and to 20.8 nMat 0.7 mMDTT. Thus, DTT-induced decline in (−)-[3H]DHA binding results from a decrease in both the number and affinity of membrane binding sites for the tracer. Receptors could be protected from DTT inactivation by preincubation with β-adrenergic ligands. Oxidants could not reverse inactivation, with the exception ofo-iodosobenzoate which was only partially effective. Thus, the β-adrenergic receptor of rabbit ventricular muscle contains essential disulfide moietie(s) which can be inactivated by reducing thiols.

 

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