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Functional characterization of coronary vascular adenosine receptors in the mouse
Author(s) -
Flood Amanda,
Headrick John P
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704170
Subject(s) - adenosine , adenosine receptor , agonist , medicine , endocrinology , chemistry , antagonist , adenosine a3 receptor , adenosine a1 receptor , receptor
Coronary responses to adenosine agonists were assessed in perfused mouse and rat hearts. The roles of nitric oxide (NO) and ATP‐dependent K + channels (K ATP ) were studied in the mouse. Resting coronary resistance was lower in mouse vs rat, as was minimal resistance (2.2±0.1 vs 3.8±0.2 mmHg ml −1 min −1 g −1 ). Peak hyperaemic flow after 20–60 s occlusion was greater in mouse. Adenosine agonists induced coronary dilation in mouse, with pEC 50 s of 9.4±0.1 for 2‐[p‐(2‐carboxyethyl)phenethylamino]‐5′‐N‐ethyl carboxamidoadenosine (CGS21680, A 2A ‐selective agonist), 9.3±0.1 for 5′‐N‐ethylcarboxamidoadenosine (NECA, A 1 /A 2 agonist), 8.4±0.1 for 2‐chloroadenosine (A 1 /A 2 agonist), 7.7±0.1 for N 6 ‐(R)‐(phenylisopropyl)adenosine (R‐PIA, A 1 /A 2B selective), and 6.8±0.2 for adenosine. The potency order (CGS21680=NECA>2‐chloroadenosine>R‐PIA>adenosine) supports A 2A adenosine receptor‐mediated dilation in mouse coronary vessels. 0.2–2 μ M of the A 2B ‐selective antagonist alloxazine failed to alter CGS21680 or 2‐chloroadenosine responses. pEC 50 s in rat were 6.7±0.2 for CGS21680, 7.3±0.1 for NECA, 7.6±0.1 for 2‐chloroadenosine, 7.2±0.1 for R‐PIA, and 6.2±0.1 for adenosine (2‐chloroadenosine>NECA=R‐PIA>CGS21680> adenosine), supporting an A 2B adenosine receptor response. NO‐synthase antagonism with 50 μ M N G ‐nitro L ‐arginine ( L ‐NOARG) increased resistance by ∼25%, and inhibited responses to CGS21680 (pEC 50 =9.0±0.1), 2‐chloroadenosine (pEC 50 =7.3±0.2) and endothelial‐dependent ADP, but not sodium nitroprusside (SNP). K ATP channel blockade with 5 μ M glibenclamide increased resistance by ∼80% and inhibited responses to CGS21680 in control (pEC 50 =8.3±0.1) and L ‐NOARG‐treated hearts (pEC 50 =7.3±0.1), and to 2‐chloroadenosine in control (pEC 50 =6.7±0.1) and L ‐NOARG‐treated hearts (pEC 50 =5.9±0.2). In summary, mouse coronary vessels are more sensitive to adenosine than rat vessels. A 2A adenosine receptors mediate dilation in mouse coronary vessels vs A 2B receptors in rat. Responses in the mouse involve a sensitive NO‐dependent response and K ATP ‐dependent dilation.British Journal of Pharmacology (2001) 133 , 1063–1072; doi: 10.1038/sj.bjp.0704170