Opioid receptor-mediated effects of interleukin-2 on the [Ca2+]i transient and contraction in isolated ventricular myocytes of the rat.
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.
Cao
Chun-Mei
CM
Department of Physiology, Zhejiang University School of Medicine, 353 Yan'an Road, Hangzhou 310031, China.
Xia
Qiang
Q
Chen
Ying-Ying
YY
Zhang
Xiong
X
Shen
Yue-Liang
YL
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
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