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.