Role of P2X3 receptor in myocardial ischemia injury and nociceptive sensory transmission

Extracellular ATP acts on purinergic receptors as a potent agonist for a variety of different cell types, including cardiomyocytes and nodose ganglia. P2X(3) receptor is the most abundant P2X-receptor subtype in heart and nodose ganglia. This study wants to observe the role of P2X(3) receptor in myocardial ischemic injury and nociceptive transmission via nodose ganglia. The serum lactate dehydrogenase (LDH), creatine kinase (CK) and CK isoform MB (CK-MB) activities were measured by automatic biochemistry analyzer. The electrocardiogram (ECG) recorded ST-segment changes and cardiac arrhythmia. The expression of P2X(3) immunoreactivity, mRNA and protein were analyzed by immunohistochemistry, in situ hybridization and western blotting. Myocardial ischemia enhanced the serum LDH, CK and CK-MB activities and caused premature beats. P2X(3) receptor antagonist A-317491 decreased the serum enzyme activities and improved premature beats in myocardial ischemic rats. The expression of P2X(3) mRNA and protein in the ischemic injury heart were higher than that in the naive heart as control. A-317491 reduced the expression of P2X(3) mRNA and protein in the myocardial ischemic injury. The myocardial ischemic injury increased the expression of P2X(3) immunoreactivity and mRNA in nodose ganglia. In rats treated with A-317491, the expression of P2X(3) immunoreactivity and mRNA in nodose ganglia was reduced. Blocking the nociceptive transmission mediated by P2X(3) receptor may protect the cardiac function. According to these results, P2X(3) receptor could be thought of as a new target for treating myocardial ischemic injury and cardiac arrhythmia and inhibiting nociceptive transmission of myocardial ischemic injury. (c) 2008 Elsevier B.V. All rights reserved.