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This Article Full Text Full Text (PDF) All Versions of this Article: 285/5/H2034    most recent 00324.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Bruck, H. Articles by Brodde, O.-E. Search for Related Content PubMed PubMed Citation Articles by Bruck, H. Articles by Brodde, O.-E.

Thr164Ile polymorphism of the human ₂-adrenoceptor exhibits blunted desensitization of cardiac functional responses in vivo

¹Departments of Pathophysiology and Nephrology, University of Essen Medical School, D-45147 Essen; and ²Institute of Pharmacology and ³Department of Anesthesiology, Martin-Luther-University of Halle, D-06097 Halle, Germany

Submitted 10 April 2003 ; accepted in final form 8 July 2003

In subjects heterozygous for Thr164Ile ₂-adrenoceptor (₂AR) polymorphism, cardiac responses to ₂AR agonist stimulation are blunted. In this study, we investigated agonist-induced desensitization of Thr164Ile ₂ARs. For this purpose, we assessed in six subjects with heterozygous Thr164Ile ₂ARs and in 10 subjects with homozygous wild-type (WT) ₂ARs the effects of 2-wk oral treatment with 3 x 5 mg/day terbutaline on terbutaline infusion-induced increases in heart rate (HR) and contractility [measured as shortening of HR-corrected duration of electromechanical systole (QS₂c)]. Compared with WT ₂AR subjects, Thr164Ile subjects exhibited a blunted terbutaline-induced maximum increase in HR (WT 32 ± 4 beats/min, Thr164Ile 19 ± 3 beats/min, P < 0.05) and contractility (WT –54 ± 2 ms, Thr164Ile –37 ± 6 ms, P < 0.05). Two-week oral terbutaline treatment desensitized cardiac ₂AR responses to terbutaline infusion (increase in HR: WT 10 ± 2 beats/min, Thr164Ile 8 ± 4 beats/min; increase in contractility: WT –22 ± 5 ms Thr164Ile: –17 ± 6 ms); however, the extent of desensitization was larger in WT than Thr164Ile ₂AR subjects. Thus, after 2-wk oral terbutaline treatment cardiac, ₂AR responses did not differ anymore between WT and Thr164Ile ₂AR subjects. We conclude that agonist-induced desensitization of cardiac ₂ARs is more pronounced in WT than Thr164Ile subjects. Thus cardiac Thr164Ile subjects appear to be somewhat protected against agonist-induced desensitization.

genetic polymorphism; heart rate; contractility

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