Kappa-opioid receptor agonist inhibits the cholera toxin-sensitive G protein in the heart.
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.
Yu
X C
XC
Department of Physiology, Faculty of Medicine, The University of Hong Kong, Hong Kong.
Diao
T M
TM
Pei
J M
JM
Zhang
W M
WM
Wong
N S
NS
Wong
T M
TM
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology*; D004558:Electric Stimulation; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011412:Propanolamines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000378:metabolism / Q000502:physiology*
D018712:Analgesics, Non-Narcotic; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D002772:Cholera Toxin; D019205:GTP-Binding Protein alpha Subunits, Gs; C033394:CGP 12177; D002118:Calcium