Kappa-opioid receptor agonist inhibits the cholera toxin-sensitive G protein in the heart

J Cardiovasc Pharmacol. 2001 Aug;38(2):232-9. doi: 10.1097/00005344-200108000-00009.


To explore the signaling mechanisms of the negative modulation of beta-adrenoceptors by kappa-Opioid receptors (kappa-OR) in the heart, the possibility of the interaction at the level of G protein and receptor was determined. Cholera toxin, an activator of the stimulatory G protein (Gs), elevated electrically induced intracellular Ca2+ ([Ca2+]i) transients and induced ribosylation of the alpha-subunit of Gs (Gsalpha) in rat ventricular myocytes. The effects were significantly attenuated by U50,488H, a specific agonist of kappa-OR, and were abolished by nor-binaltorphimine, a selective kappa-OR antagonist. The content of Gsalpha, however, was not affected by U50,488H. Receptor binding experiments showed that neither Bmax nor Kd of the binding of [3H]CGP-12177, a beta-adrenoceptor antagonist, was affected by U50,488H. The current study provides the first evidence that kappa-OR stimulation inhibits the ribosylation of the alpha-subunit of the Gs protein, thus inhibiting the action of cholera toxin on the protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / pharmacology
  • Analgesics, Non-Narcotic / pharmacology
  • Animals
  • Binding Sites
  • Calcium / metabolism
  • Cholera Toxin / pharmacology*
  • Electric Stimulation
  • GTP-Binding Protein alpha Subunits, Gs / antagonists & inhibitors*
  • GTP-Binding Protein alpha Subunits, Gs / metabolism*
  • Heart Ventricles / cytology
  • Heart Ventricles / drug effects
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Propanolamines / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, beta / metabolism
  • Receptors, Opioid, kappa / agonists*
  • Receptors, Opioid, kappa / metabolism
  • Receptors, Opioid, kappa / physiology*


  • Analgesics, Non-Narcotic
  • Propanolamines
  • Receptors, Adrenergic, beta
  • Receptors, Opioid, kappa
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Cholera Toxin
  • GTP-Binding Protein alpha Subunits, Gs
  • CGP 12177
  • Calcium