Attenuated "cross talk" between kappa-opioid receptors and beta-adrenoceptors in the heart of chronically hypoxic rats

Pflugers Arch. 2002 May;444(1-2):126-32. doi: 10.1007/s00424-002-0814-0. Epub 2002 Mar 9.

Abstract

At 0.1-1 microM, U50488H, a kappa-opioid receptor agonist, inhibited the stimulatory effects of 1 microM isoprenaline, a beta-adrenoceptor agonist, on the electrically induced intracellular Ca2+ ([Ca2+](i)) transient and cAMP accumulation ("cross talk" between kappa-opioid receptors and beta-adrenoceptors) in the presence of 1 microM ICI118,551, a beta(2)-adrenoceptor antagonist in ventricular myocytes from both normoxic and chronically hypoxic rats. Pretreatment with 20 microg/ml cholera toxin increased the ADP-ribosylation of Gsalpha subunits and the electrically induced [Ca2+](i) transient in both normoxic and chronically hypoxic rats. The effects of cholera toxin were inhibited by 1 microM U50488H and the inhibitory effect of U50488H was attenuated in chronically hypoxic rats. Similarly, 1 microM forskolin also increased the electrically induced [Ca2+](i) transient and cAMP accumulation, which were both inhibited by U50488H, in both normoxic and chronically hypoxic rats. The inhibitory effects of 1 microM U50488H were significantly attenuated in chronically hypoxic rats. The results are novel findings, in that the "cross talk" between kappa-opioid receptors and beta-adrenoceptors is attenuated following chronic hypoxia. The attenuation may be due to decreased responses of Gs-protein and adenylyl cyclase to kappa-opioid receptor activation in addition to desensitization of the receptor itself.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate Ribose / metabolism
  • Adenylyl Cyclases / metabolism
  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Calcium Signaling / drug effects
  • Cardiomegaly / physiopathology
  • Cholera Toxin / pharmacology
  • Chronic Disease
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism
  • Dose-Response Relationship, Drug
  • Fluorescent Dyes
  • Fura-2
  • GTP-Binding Protein alpha Subunits, Gs / metabolism
  • Heart / physiopathology*
  • Hypoxia / physiopathology*
  • In Vitro Techniques
  • Isoproterenol / pharmacology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptor Cross-Talk / physiology*
  • Receptors, Adrenergic, beta / physiology*
  • Receptors, Opioid, kappa / physiology*

Substances

  • Adrenergic beta-Agonists
  • Fluorescent Dyes
  • Receptors, Adrenergic, beta
  • Receptors, Opioid, kappa
  • Colforsin
  • Adenosine Diphosphate Ribose
  • Cholera Toxin
  • Cyclic AMP
  • GTP-Binding Protein alpha Subunits, Gs
  • Adenylyl Cyclases
  • Isoproterenol
  • Fura-2