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Am J Physiol Heart Circ Physiol (July 17, 2003). doi:10.1152/ajpheart.00324.2003
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Submitted on April 10, 2003
Accepted on July 8, 2003

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

Heike Bruck1, Kirsten Leineweber1, Anke Ulrich2, Joachim Radke2, Gerd Heusch3, Thomas Philipp3, and Otto-Erich Brodde1*

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

* To whom correspondence should be addressed. E-mail: otto-erich.brodde{at}uni-essen.de.

In subjects heterozygous for the Thr164Ile {beta}2 -adrenoceptor ({beta}2AR) polymorphism cardiac responses to {beta}2AR-agonist stimulation are blunted. In this study we investigated agonist-induced desensitization of the Thr164Ile {beta}2AR. For this purpose we assessed in 6 subjects heterozygous Thr164Ile and in 10 subjects homozygous wild-type (WT) {beta}2AR the effects of two weeks oral treatment with 3x5mg/ day terbutaline (TER) on TER-infusion induced increases in heart rate (HR) and contractility (measured as shortening of HR-corrected duration of electromechanical systole, QS2c). Compared to WT {beta}2AR subjects, Thr164Ile subjects exhibited a blunted TER-induced maximum increase in HR (WT 32±4 bpm, Thr164Ile 19±3 bpm; p<0.05) and contractility (WT -54±2 ms, Thr164Ile -37±6 ms; p<0.05). Two weeks oral TER-treatment desensitized cardiac {beta}2AR responses to TER-infusion (increase in HR WT: 10±2, Thr164Ile: 8±4 bpm; in contractility WT: -22±5, Thr164Ile: -17±6 ms); however, the extent in desensitization was larger in WT than in Thr164Ile {beta}2AR subjects. Thus, after 2 weeks oral TER-treatment cardiac {beta}2AR responses did not differ anymore between WT and Thr164Ile {beta}2AR subjects. We conclude that agonist-induced desensitization of cardiac {beta}2AR is more pronounced in WT than in Thr164Ile subjects. Thus, cardiac Thr164Ile appear to be somewhat protected against agonist-induced desensitization.




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