%0 Journal Article %T Signaling pathway mediated by kappa-opioid receptor is impaired in cardiac hypertrophy %A Pei Jian-Ming %A Wang Yue-Min %A Zhu Yun-Long %A Chen Mai %A Huang De-Ming %J Acta Pharmacologica Sinica %D 2016 %B 2016 %9 %! Signaling pathway mediated by kappa-opioid receptor is impaired in cardiac hypertrophy %K %X Aim: The responses of the intracellular calcium ([Ca2+]i) and the intracellular pH (pHi) to kappa-opioid receptor stimulation were determined in the single right ventricular myocytes isolated from the hearts of chronically hypoxic rats which exhibited right ventricular hypertrophy (RVH). Methods: With the spectrofluorometric method, the electrically-induced [Ca2+]i transient and pHi were measured in myocytes loaded with fura-2 and BCECF [2',7'-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorscein], respectively. Results: U50,488H, a selective kappa-opioid agonist decreased the electrically-induced [Ca2+]i transient and increased the pHi. The effect of U50,488H was mediated by protein kinase C (PKC). In the RVH, the effect of U50,488H on the [Ca2+]i transient and the pHi were significantly attenuated. In parallel, 4-phorbol 12-myristate 13-acetate (PMA), an activator of PKC, also decreased the [Ca2+]i transient and increased the pHi. In the RVH, the effects of PMA were blunted. The recovery of pHi, which was blocked by ethylisopropyl-amiloride (EIPA), following an acid loading induced by washout of 10 mmol/L NH4)Cl exposing to the cells for 10 min was the same in the RVH and control myocytes. Conclusion: kappa-Opioid receptor signaling was impaired in the cardiac hypertrophy due to a defect in the coupling of PKC signaling with its effector. %U http://www.chinaphar.com/article/view/7631 %V 22 %N 10 %P 887-895 %@ 1745-7254