title: Role of δ2 opioid receptor in cardioprotection against hypoxia-reoxygenation injury.
abstract: Several lines of in vivo evidence demonstrated that activation of δ-opioid receptors (ORs) with agonists mimics the cardioprotective effect of ischemic preconditioning. However, the subtypes of ORs involved and the molecular and cellular mechanisms are not entirely clear. To investigate the significance of the contribution by δ ORs to cardiomyocyte survival, we used an in vitro model of hypoxia/reoxygenation (H/R) in primary cultures of neonatal rat cardiomyocytes to study the role of different δ ORs in cardiomyocyte apoptosis and the relevant downstream signaling pathway. The results showed that apoptosis in neonatal cardiomyocytes induced by H/R was reversed by δ2 OR agonist, deltorphin E but not by δ1 OR agonist DPDPE; the deltorphin E-induced cytoprotection was totally abrogated by the MEK inhibitor PD98059 and overexpression of dominant interfering form of MEK1; in contrast, overexpression of constitutive active form of MEK1 exerted a similar protective effect as deltorphin E. These results suggest that δ2 OR, but not δ1 OR, plays a key role in preventing cardiomyocytes from apoptosis during H/R injury, which is mainly mediated by the MEK/ERK1/2 pathway.
authors.affiliation: Department of Emergency Medicine, Zhongshan Hospital, FuDan University Shanghai, China. anashen@yeah.net
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
authors.forename: Qiwen
authors.initials: Q
authors.lastname: Ben
authors.forename: Yaping
authors.initials: Y
authors.lastname: Zhang
authors.forename: Genxi
authors.initials: G
authors.lastname: Jiang
authors.forename: Chenling
authors.initials: C
authors.lastname: Yao
authors.forename: Dongwei
authors.initials: D
authors.lastname: Shi
authors.forename: Zhan
authors.initials: Z
authors.lastname: Sun
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Tong
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000502:physiology*
chemical_list: D017465:Receptors, Opioid, delta; D016308:Enkephalin, Leucine-2-Alanine