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Human atrial β(1L)-adrenoceptor but not β₃-adrenoceptor activation increases force and Ca(2+) current at physiological temperature.
- Source :
-
British journal of pharmacology [Br J Pharmacol] 2011 Feb; Vol. 162 (4), pp. 823-39. - Publication Year :
- 2011
-
Abstract
- Background and Purpose: It has been proposed that BRL37344, SR58611 and CGP12177 activate β₃-adrenoceptors in human atrium to increase contractility and L-type Ca(2+) current (I(Ca-L)). β₃-adrenoceptor agonists are potentially beneficial for the treatment of a variety of diseases but concomitant cardiostimulation would be potentially harmful. It has also been proposed that (-)-CGP12177 activates the low affinity binding site of the β₁-adrenoceptor in human atrium. We therefore used BRL37344, SR58611 and (-)-CGP12177 with selective β-adrenoceptor subtype antagonists to clarify cardiostimulant β-adrenoceptor subtypes in human atrium.<br />Experimental Approach: Human right atrium was obtained from patients without heart failure undergoing coronary artery bypass or valve surgery. Cardiomyocytes were prepared to test BRL37344, SR58611 and CGP12177 effects on I(Ca-L). Contractile effects were determined on right atrial trabeculae.<br />Key Results: BRL37344 increased force which was antagonized by blockade of β₁- and β₂-adrenoceptors but not by blockade of β₃-adrenoceptors with β₃-adrenoceptor-selective L-748,337 (1 µM). The β₃-adrenoceptor agonist SR58611 (1 nM-10 µM) did not affect atrial force. BRL37344 and SR58611 did not increase I(Ca-L) at 37°C, but did at 24°C which was prevented by L-748,337. (-)-CGP12177 increased force and I(Ca-L) at both 24°C and 37°C which was prevented by (-)-bupranolol (1-10 µM), but not L-748,337.<br />Conclusions and Implications: We conclude that the inotropic responses to BRL37344 are mediated through β₁- and β₂-adrenoceptors. The inotropic and I(Ca-L) responses to (-)-CGP12177 are mediated through the low affinity site β(1L)-adrenoceptor of the β₁-adrenoceptor. β₃-adrenoceptor-mediated increases in I(Ca-L) are restricted to low temperatures. Human atrial β₃-adrenoceptors do not change contractility and I(Ca-L) at physiological temperature.<br /> (© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.)
- Subjects :
- Adrenergic beta-Agonists pharmacology
Adrenergic beta-Antagonists pharmacology
Aged
Atrial Appendage cytology
Calcium Signaling drug effects
Ethanolamines antagonists & inhibitors
Ethanolamines pharmacology
Female
Humans
In Vitro Techniques
Kinetics
Male
Middle Aged
Myocytes, Cardiac metabolism
Propanolamines antagonists & inhibitors
Propanolamines pharmacology
Receptors, Adrenergic, beta-3 metabolism
Temperature
Tetrahydronaphthalenes antagonists & inhibitors
Tetrahydronaphthalenes pharmacology
Calcium Channels, L-Type metabolism
Myocardial Contraction drug effects
Myocytes, Cardiac drug effects
Receptors, Adrenergic, beta-1 metabolism
Receptors, Adrenergic, beta-2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5381
- Volume :
- 162
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- British journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 20726983
- Full Text :
- https://doi.org/10.1111/j.1476-5381.2010.00996.x