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A Novel Skeletal Muscle Cytoprotective Action of Adenosine A3 Receptors
Author(s) -
Zheng Jingang,
Wang Rubio,
Zambraski Edward,
Wu Dan,
Jacobson Kenneth,
Liang Bruce
Publication year - 2007
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.21.6.a800-a
Subject(s) - ccpa , skeletal muscle , agonist , receptor , adenosine a1 receptor , medicine , adenosine receptor , endocrinology , adenosine , adenosine a3 receptor , pharmacology , receptor antagonist , chemistry , antagonist
Adenosine (Ado) can protect skeletal muscle from ischemic injury, in addition to its cardio‐ and vasculo‐protective effect. However, identity of the Ado receptor and the mechanism mediating skeletal muscle protection is unknown. Using a quantitative mouse hindlimb ischemia‐reperfusion injury model, the objective here was to assess the protective role of Ado receptor subtypes. Ado A3 receptor‐selective agonist Cl‐IBMECA reduced skeletal muscle injury, an effect that was blocked by the A3 receptor antagonist MRS1191 (% injury, vehicle: 28±5.9% vs. Cl‐IBMECA: 5.4±3.8%, Cl‐IBMECA & MRS1191: 21.5±3.5%, mean±SE, 7–22 mice, ANOVA & comparisons, Cl‐IBMECA vs. all others, P<0.05). The A1 receptor agonist CCPA was also protective and and was selectively antagonized by the A1 receptor blocker DPCPX (CCPA: 10.8±1.8%, DPCPX &CCPA: 22±3.3%, 7–12 mice, P<0.05). The protection induced by Cl‐IBMECA and another A3 receptor agonist MRS3558 was completely abrogated in phospholipase C β2/3‐null mice while that caused by CCPA remained unaffected in these animals (8–10 mice). The study demonstrated a novel potent protective effect of A3 receptors in skeletal muscle and implicates phospholipase C β in mediating this protection. The data add to the cyto‐protective actions of adenosine and suggest that the A3 receptor is a novel therapeutic target in ameliorating skeletal muscle injury.