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Modulation of the cardiac β‐adrenergic contractile response by adenosine A1 and A2a receptors: evidence for receptor interactions
Author(s) -
Chandrasekera P. Charukeshi,
McIntosh Victoria J.,
Cao Frank,
Lasley Robert D.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.769.5
Subject(s) - ccpa , contractility , agonist , medicine , endocrinology , adenosine , adenosine receptor , receptor , chemistry , chronotropic , cgs 21680 , heart rate , blood pressure
Mammalian myocardium expresses four adenosine receptor (AR) subtypes (A1, A2a, A2b, & A3). A1AR inhibits the β‐adrenergic receptor‐mediated positive inotropy, but the role of A2aAR in altering cardiac contractility is controversial. The objective of this study was to determine the effects of A2aAR on A1AR‐anti‐adrenergic response. Experiments were conducted in wild type (WT) and A2a‐knock‐out (KO) isolated perfused mouse hearts by measuring left ventricular systolic pressure (LVSP), +dP/dt, & −dP/dt. A2aAR agonist CGS‐21680 alone did not alter contractility or the isoproterenol (ISO)‐induced contractile response. Effects of 200nM CCPA pre‐treatment on 2 nM ISO are shown below (n≥4, data expressed as % increase from baseline, *p<0.05 CCPA+ISO vs ISO, # p<0.05 KO‐CCPA+ISO vs WT‐CCPA+ISO):LVSP +dP/dt −dP/dtWT‐ISO 76±4 109±7 133±7 WT‐CCPA+ISO 35±4* 48±4* 56±5* KO‐ISO 86±8 129±10 154±9 KO‐CCPA+ISO 16±3* # 19±4* # 31±5* #Reversing the sequence of agonist infusion (i.e. ISO, then CCPA) significantly reduced the A1AR anti‐adrenergic response. These results indicate that anti‐adrenergic effects of A1AR are potentiated in the absence of A2aAR, and that A1AR pre‐activation is necessary to elicit the full anti‐adrenergic response. Since A2aAR only alters contractility indirectly, these data suggest that receptor cross‐talk/direct receptor interactions may account for the observed contractile response.