title: Signaling pathway mediated by kappa-opioid receptor is impaired in cardiac hypertrophy.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  kappa-Opioid receptor signaling was impaired in the cardiac hypertrophy due to a defect in the coupling of PKC signaling with its effector.
authors.affiliation: Department of Physiology, Xijin Hospital, Fourth Military Medical University, Xi-an 710032, China. jmpei8@fmmu.edu.cn
authors.forename: J M
authors.initials: JM
authors.lastname: Pei
authors.forename: Y M
authors.initials: YM
authors.lastname: Wang
authors.forename: Y L
authors.initials: YL
authors.lastname: Zhu
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.forename: T M
authors.initials: TM
authors.lastname: Wong
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006332:Cardiomegaly / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D017473:Receptors, Opioid, kappa; D011493:Protein Kinase C; D002118:Calcium