biostudies-literatureFu LWNCCIH NIH HHSU.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood InstituteU.S. Department of Health & Human Services | NIH | National Center for Complementary and Integrative HealthU.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)17224https://www.ebi.ac.uk/biostudies/studies/S-EPMC6868205biostudies-literatureUnknown9(1)Myocardial ischemia evokes powerful reflex responses through activation of vagal and sympathetic afferents in the heart through the release of ischemic metabolites. We have demonstrated that extracellular ATP stimulates cardiac sympathetic afferents through P2 receptor-mediated mechanism, and that opioid peptides suppress these afferents' activity. However, the roles of both P2 receptor and endogenous opioids in cardiac sympathoexcitatory reflex (CSR) responses remain unclear. We therefore hypothesized that activation of cardiac P2 receptor evokes CSR responses by stimulating cardiac sympathetic afferents and these CSR responses are modulated by endogenous opioids. We observed that intrapericardial injection of α,β-methylene ATP (α,β-meATP, P2X receptor agonist), but not ADP (P2Y receptor Scientific reportsRole of opioid receptors in modulation of P2X receptor-mediated cardiac sympathoexcitatory reflex response.PMC6868205HL-66217R01 AT009347AT009347Malik STjen-A-Looi SCGuo ZLFu LWBarvarz SfalseRole of opioid receptors in modulation of P2X receptor-mediated cardiac sympathoexcitatory reflex response.Myocardial ischemia evokes powerful reflex responses through activation of vagal and sympathetic afferents in the heart through the release of ischemic metabolites. We have demonstrated that extracellular ATP stimulates cardiac sympathetic afferents through P2 receptor-mediated mechanism, and that opioid peptides suppress these afferents' activity. However, the roles of both P2 receptor and endogenous opioids in cardiac sympathoexcitatory reflex (CSR) responses remain unclear. We therefore hypothesized that activation of cardiac P2 receptor evokes CSR responses by stimulating cardiac sympathetic afferents and these CSR responses are modulated by endogenous opioids. We observed that intrapericardial injection of α,β-methylene ATP (α,β-meATP, P2X receptor agonist), but not ADP (P2Y receptor 2019-01-01T00:00:00Z2019 Nov2025-04-18T13:36:42.34Z2020-05-21T20:36:20ZS-EPMC68682053174856910.1038/s41598-019-53754-6