title: Opioid receptor-mediated effects of interleukin-2 on the [Ca2+]i transient and contraction in isolated ventricular myocytes of the rat.
abstract: Cytokines play significant roles in some cardiovascular disorders, but direct myocardial effects of cytokines remain to be elucidated. In this study, we examined the effects and possible mechanisms of interleukin-2 (IL-2) on contraction and the [Ca2+]i transient of enzymatically isolated ventricular myocytes with spectrofluorometry and video tracking. IL-2 (2.5-200 U/ml) depressed both the contraction and the [Ca2+]i transient in a dose-dependent manner. Pretreatment with the universal opioid receptor antagonist naloxone (10 nM), or a specific kappa opioid receptor antagonist, nor-binaltorphimine (nor-BNI, 10 nM), abolished the inhibitory effect of IL-2 on contraction and the [Ca2+]i transient; the specific delta-opioid receptor antagonist naltrindole (1 microM) had no effect. The effect of IL-2 was also abolished after pretreatment with pertussis toxin (PTX, 5 mg/l), but not by genistein (100 microM). Pretreatment with the phospholipase C inhibitor U73122 (5 microM) significantly inhibited the IL-2-induced depression of contraction and the [Ca2+]i transient. It is concluded that the effects of IL-2 on contraction and the [Ca2+]i transient of ventricular myocytes are mediated via the cardiac kappa opioid receptor, and the postreceptor signal transduction pathway includes a PTX-sensitive G protein and phospholipase C.
authors.affiliation: Department of Physiology, Zhejiang University School of Medicine, 353 Yan'an Road, Hangzhou 310031, China.
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Cao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Chen
authors.forename: Xiong
authors.initials: X
authors.lastname: Zhang
authors.forename: Yue-Liang
authors.initials: YL
authors.lastname: Shen
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology; D007376:Interleukin-2 / Q000494:pharmacology*; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D018712:Analgesics, Non-Narcotic; D007376:Interleukin-2; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium