Agonist‐specific activation of the <i>β</i>₂‐adrenoceptor/G_s‐protein and <i>β</i>₂‐adrenoceptor/G_i‐protein pathway in adult rat ventricular cardiomyocytes

• Klaus Pönicke

• Ferdinand Gröner

• Ingrid Heinroth‐Hoffmann

• Otto‐Erich Brodde

抄録

<jats:list list-type="explicit-label"> In rat ventricular cardiomyocytes β 2 ‐adrenoceptors (AR) couple to G s ‐ and G i ‐protein, and evidence has accumulated that β 2 ‐AR agonists can differentially activate either G s ‐ or G s ‐ and G i ‐protein. In this study, in isolated adult rat ventricular cardiomyocytes, we assessed the effects of pertussis toxin (PTX) on β 2 ‐AR agonist (terbutaline (TER), salbutamol (SAL) and fenoterol (FEN)) evoked inhibition of phenylephrine (PE)‐induced increase in the rate of protein synthesis (assessed as [ 3 H]phenylalanine incorporation) to find out which β 2 ‐AR agonist activates selectively G s ‐ or G s ‐ and G i ‐protein. PE (1  μ M ) increased the rate of protein synthesis from 100% to 130±2% ( n =34). FEN, TER and SAL (1 n M –10  μ M ) inhibited PE‐induced increase in the rate of protein synthesis concentration‐dependently. FEN inhibited PE effects almost completely (from 132±3 to 101±1%), whereas TER and SAL caused only partial inhibition (from 131±2 to 114±2 and 129±1 to 111±2%, respectively). Pretreatment of cardiomyocytes with PTX (250 ng ml −1 for 16 h at 37°C) did not affect FEN effects, but converted TER‐ and SAL‐evoked partial inhibition into complete inhibition. Inhibitory effects of the three β 2 ‐AR agonists were markedly attenuated by β 1 ‐AR selective antagonist CGP 20712A (CGP) (300 n M ); in contrast, β 2 ‐AR selective antagonist ICI 118,551 (55 n M ) inhibited the inhibitory effects of the three β 2 ‐AR agonists only in PTX‐pretreated cardiomyocytes, with β 1 ‐AR blocked by CGP. We conclude that, in adult rat ventricular cardiomyocytes, FEN activates selectively the G s protein‐pathway, while TER and SAL activate the G s ‐ and G i ‐protein pathways. Part of the effects of these three β 2 ‐AR agonists appears to be mediated by β 1 ‐AR. British Journal of Pharmacology (2006) 147 , 714–719. doi:<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" xlink:href="10.1038/sj.bjp.0706674">10.1038/sj.bjp.0706674

収録刊行物

• British Journal of Pharmacology

  British Journal of Pharmacology 147 (7), 714-719, 2006-04

  Wiley

キーワード

• Pharmacology

詳細情報

• CRID: 1363388844898789376
• NII論文ID: 30022967197
• DOI: 10.1038/sj.bjp.0706674
• ISSN: 14765381
• ISSN: 00071188
• Web Site: https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1038%2Fsj.bjp.0706674
• Web Site: https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1038/sj.bjp.0706674
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