Human atrial β 1L-adrenoceptor but not β 3- adrenoceptor activation increases force and Ca 2+ current at physiological temperature

Christ, Torsten, Molenaar, Peter, Klenowski, Paul M., Ravens, Ursula and Kaumann, Alberto J. (2011) Human atrial β 1L-adrenoceptor but not β 3- adrenoceptor activation increases force and Ca 2+ current at physiological temperature. British Journal of Pharmacology, 162 4: 823-839. doi:10.1111/j.1476-5381.2010.00996.x


Author Christ, Torsten
Molenaar, Peter
Klenowski, Paul M.
Ravens, Ursula
Kaumann, Alberto J.
Title Human atrial β 1L-adrenoceptor but not β 3- adrenoceptor activation increases force and Ca 2+ current at physiological temperature
Journal name British Journal of Pharmacology   Check publisher's open access policy
ISSN 0007-1188
1476-5381
Publication date 2011-01-01
Sub-type Article (original research)
DOI 10.1111/j.1476-5381.2010.00996.x
Open Access Status Not Open Access
Volume 162
Issue 4
Start page 823
End page 839
Total pages 17
Place of publication West Sussex, United Kingdom
Publisher John Wiley & Sons
Subject 3004 Pharmacology
Formatted abstract
Background and Purpose
It has been proposed that BRL37344, SR58611 and CGP12177 activate β 3-adrenoceptors in human atrium to increase contractility and L-type Ca 2+ current (I Ca-L). β 3-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 β 1-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.
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.
Key Results
BRL37344 increased force which was antagonized by blockade of β 1- and β 2-adrenoceptors but not by blockade of β 3- adrenoceptors with β 3-adrenoceptor-selective L-748,337 (1 ÂμM). The β 3-adrenoceptor agonist SR58611 (1 nM-10 ÂμM) 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 ÂμM), but not L-748,337.
Conclusions and Implications
We conclude that the inotropic responses to BRL37344 are mediated through β 1- and β 2- adrenoceptors. The inotropic and I Ca-L responses to (-)-CGP12177 are mediated through the low affinity site β 1L-adrenoceptor of the β 1-adrenoceptor. β 3-adrenoceptor-mediated increases in I Ca-L are restricted to low temperatures. Human atrial β 3-adrenoceptors do not change contractility and I Ca-L at physiological temperature.
Keyword β 1L- adrenoceptors
β 3-adrenoceptors
(-)-bupranolol
(-)-CGP12177
BRL37344
human atrial force and I Ca-L
L-748,337
SR58611
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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