Pei J M, Zhou J J, Bian J S, Yu X C, Fung M L, Wong T M
Department of Physiology and Institute of Cardiovascular Sciences and Medicine, Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Am J Physiol Cell Physiol. 2000 Nov;279(5):C1483-94. doi: 10.1152/ajpcell.2000.279.5.C1483.
kappa-Opioid receptor (kappa-OR) stimulation with U50,488H, a selective kappa-OR agonist, or activation of protein kinase C (PKC) with 4-phorbol 12-myristate 13-acetate (PMA), an activator of PKC, decreased the electrically induced intracellular Ca(2+) (Ca(2+)) transient and increased the intracellular pH (pH(i)) in single ventricular myocytes of rats subjected to 10% oxygen for 4 wk. The effects of U50,488H were abolished by nor-binaltorphimine, a selective kappa-OR antagonist, and calphostin C, a specific inhibitor of PKC, while the effects of PMA were abolished by calphostin C and ethylisopropylamiloride (EIPA), a potent Na(+)/H(+) exchange blocker. In both right hypertrophied and left nonhypertrophied ventricles of chronically hypoxic rats, the effects of U50,488H or PMA on Ca(2+) transient and pH(i) were significantly attenuated and completely abolished, respectively. Results are first evidence that the Ca(2+) and pH(i) responses to kappa-OR stimulation are attenuated in the chronically hypoxic rat heart, which may be due to reduced responses to PKC activation. Responses to all treatments were the same for right and left ventricles, indicating that the functional impairment is independent of hypertrophy. kappa-OR mRNA expression was the same in right and left ventricles of both normoxic and hypoxic rats, indicating no regional specificity.
用选择性κ-阿片受体激动剂U50,488H刺激κ-阿片受体（κ-OR），或用蛋白激酶C（PKC）激活剂4-佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）激活PKC，可降低在10%氧气环境中饲养4周的大鼠单个心室肌细胞中电诱导的细胞内Ca²⁺（[Ca²⁺]i）瞬变，并提高细胞内pH（pH i）。选择性κ-阿片受体拮抗剂nor-binaltorphimine和PKC特异性抑制剂钙泊三醇C可消除U50,488H的作用，而钙泊三醇C和强效Na⁺/H⁺交换阻滞剂乙基异丙基amiloride（EIPA）可消除PMA的作用。在慢性低氧大鼠的右心室肥厚和左心室非肥厚区域，U50,488H或PMA对[Ca²⁺]i瞬变和pH i的作用分别显著减弱和完全消除。结果首次证明，在慢性低氧大鼠心脏中，对κ-阿片受体刺激的[Ca²⁺]i和pH i反应减弱，这可能是由于对PKC激活的反应降低所致。左右心室对所有处理的反应相同，表明功能损害与肥厚无关。在常氧和低氧大鼠的左右心室中，κ-阿片受体mRNA表达相同，表明无区域特异性。
