Genotype-dependent time course of lymphocyte β2-adrenergic receptor down-regulation

被引:33
作者
Bruck, H
Leineweber, K
Beilfuss, A
Weber, M
Heusch, G
Philipp, T
Brodde, OE
机构
[1] Univ Essen Gesamthsch, Sch Med, Dept Pathophysiol, D-45147 Essen, Germany
[2] Univ Essen Gesamthsch, Sch Med, Dept Nephrol, D-45147 Essen, Germany
关键词
D O I
10.1016/S0009-9236(03)00188-7
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background: Volunteers homozygous for Glu27 beta(2)-adrenergic receptor (beta(2)AR) polymorphism have delayed onset of agonist-induced desensitization of cardiac beta(2)AR responses. Methods and Results. To determine whether this can also be demonstrated for Glu27Glu beta(2)AR natively expressed in circulating lymphocytes, we assessed the effects of 2 weeks of oral treatment with 3 x 5 mg/d terbutaline on lymphocyte beta(2)AR density (determined by [-] - [iodine 125]iodocyanopindolol binding) and responsiveness (assessed as [-] -isoproterenol hydrochloride [INN, isoprenaline] [ 1 nmol/L to 1 mumol/L]-induced lymphocyte cyclic adenosine monophosphate increases) in 23 healthy volunteers (13 with wild-type beta(2)AR [group A], 5 homozygous for Glu27 with Gly16Gly or Arg16Gly [group B], and 5 homozygous for Gly16 with Gln27Gln or Gln27Glu [group C]). Before terbutaline treatment, lymphocyte beta(2)AR density and isoproterenol-induced lymphocyte cyclic adenosine monophosphate accumulation were not significantly different in the genotype groups; 2 weeks of terbutaline treatment significantly decreased lymphocyte beta(2)AR density and responsiveness in the 3 genotype groups to a nearly identical extent, and no differences were observed. In time-course studies, however, in groups A and C lymphocyte beta(2)AR showed significant (P < .05, repeated-measures ANOVA) down-regulation as early as 24 hours after the first terbutaline intake, whereas in group B significant (P < .05, repeated-measures ANOVA) beta(2)AR decreases were observed only 72 hours after the first terbutaline intake. Thus the time course of lymphocyte beta(2)AR down-regulation in group B was significantly (P < .01, 2-way ANOVA) different from that in groups A and C. Conclusion: The extent of lymphocyte beta(2)AR down-regulation after long-term terbutaline treatment in volunteers homozygous for the Gly16 or Glu27 beta(2)AR polymorphism was genotype-independent and was nearly identical to that in wild-type beta(2)AR volunteers. However, the onset of beta(2)AR down-regulation was delayed in volunteers homozygous for the Glu27 beta(2)AR polymorphism.
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页码:255 / 263
页数:9
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