Chronic opiate receptor activation in vivo alters the level of G-protein subunits in guinea-pig myenteric plexus.
Studies with the longitudinal muscle-myenteric plexus preparation of the guinea-pig ileum were undertaken to investigate the relationship between guanine nucleotide-binding proteins (G-proteins) and chronic opioid receptor activation in vivo. Treatment with the narcotic agonist fentanyl, at doses which render the preparation tolerant and dependent, led to an increase of pertussis toxin-catalysed incorporation of ADP-ribose in a protein of approximately 40,000 mol. wt. Quantitative immunoblotting, using site-directed antisera, demonstrated an upregulation of G alpha i/G alpha o and, to an even greater degree, of G beta. However, the level of G alpha s was decreased by the same treatment. All alterations observed were abolished by the concomitant presence of the antagonist naloxone. The implications of this differential regulation of G-protein subunits for opiate-induced tolerance and dependence are discussed.
Lang
J
J
Max-Planck-Institut für Psychiatrie, Abt. Neuropharmacokologie, Martinsried, F.R.G.
Schulz
R
R
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D005283:Fentanyl / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006168:Guinea Pigs; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*
D011957:Receptors, Opioid; D000246:Adenosine Diphosphate Ribose; D019204:GTP-Binding Proteins; D005283:Fentanyl