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The role of muscarinic receptors in the beneficial effects of adenosine against myocardial reperfusion injury in rats
- Source :
- PLoS ONE, PLoS ONE, Vol 6, Iss 11, p e25618 (2011)
- Publication Year :
- 2011
-
Abstract
- Adenosine, a catabolite of ATP, displays a wide variety of effects in the heart including regulation of cardiac response to myocardial ischemia and reperfusion injury. Nonetheless, the precise mechanism of adenosine-induced cardioprotection is still elusive. Isolated Sprague-Dawley rat hearts underwent 30 min global ischemia and 120 min reperfusion using a Langendorff apparatus. Both adenosine and acetylcholine treatment recovered the post-reperfusion cardiac function associated with adenosine and muscarinic receptors activation. Simultaneous administration of adenosine and acetylcholine failed to exert any additive protective effect, suggesting a shared mechanism between the two. Our data further revealed a cross-talk between the adenosine and acetylcholine receptor signaling in reperfused rat hearts. Interestingly, the selective M(2) muscarinic acetylcholine receptor antagonist methoctramine significantly attenuated the cardioprotective effect of adenosine. In addition, treatment with adenosine upregulated the expression and the maximal binding capacity of muscarinic acetylcholine receptor, which were inhibited by the selective A(1) adenosine receptor antagonist 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX) and the nitric oxide synthase inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME). These data suggested a possible functional coupling between the adenosine and muscarinic receptors behind the observed cardioprotection. Furthermore, nitric oxide was found involved in triggering the response to each of the two receptor agonist. In summary, there may be a cross-talk between the adenosine and muscarinic receptors in ischemic/reperfused myocardium with nitric oxide synthase might serve as the distal converging point. In addition, adenosine contributes to the invigorating effect of adenosine on muscarinic receptor thereby prompting to regulation of cardiac function. These findings argue for a potentially novel mechanism behind the adenosine-mediated cardioprotection.
- Subjects :
- Male
medicine.medical_specialty
Adenosine
Anatomy and Physiology
Myocardial Infarction
lcsh:Medicine
Myocardial Reperfusion Injury
In Vitro Techniques
Adenosine receptor antagonist
Nitric Oxide
Cardiovascular
Cardiovascular System
Biochemistry
Cardiovascular Pharmacology
Rats, Sprague-Dawley
Adenosine A1 receptor
Radioligand Assay
Model Organisms
Internal medicine
medicine
Animals
lcsh:Science
Biology
Multidisciplinary
Chemistry
lcsh:R
Hemodynamics
Muscarinic acetylcholine receptor M3
Proteins
Muscarinic acetylcholine receptor M2
Neurochemistry
Animal Models
Purinergic signalling
Adenosine A3 receptor
Adenosine receptor
Receptors, Muscarinic
Acetylcholine
Rats
Endocrinology
Muscarinic Acetylcholine Receptors
Rat
Medicine
lcsh:Q
Neurochemicals
Adenosine A2B receptor
Research Article
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 6
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....7a4b541963ae12ade1888f57e5a736bb