Opioid receptor-mediated effects of interleukin-2 on the [Ca²]_i transient and contraction in isolated ventricular myocytes of the rat.

Cao, Chun-Mei; Xia, Qiang; Chen, Ying-Ying; Zhang, Xiong; Shen, Yue-Liang

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 κ 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 δ-opioid receptor antagonist naltrindole (1 µM) 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 µM). Pretreatment with the phospholipase C inhibitor U73122 (5 µM) 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 κ opioid receptor, and the postreceptor signal transduction pathway includes a PTX-sensitive G protein and phospholipase C.

CYTOKINES; CARDIOVASCULAR diseases; INTERLEUKIN-2; MUSCLE cells; OPIOID receptors; PHOSPHOLIPASE C

Pflügers Archiv: European Journal of Physiology, 2002, Vol 443, Issue 4, p635

0031-6768

Academic Journal

10.1007/s00424-001-0743-3