Regulation of G proteins by chronic opiate and clonidine treatment in the guinea pig myenteric plexus

H Ammer, L Nice, J Lang and R Schulz

Institute of Pharmacology, Toxicology and Pharmacy, University of Munich, Federal Republic of Germany.

G proteins have been implicated in the development of opioid dependence of the guinea pig myenteric plexus as chronic fentanyl elevates G0/i alpha and pertussis toxin prevents this phenomenon. Therefore, the present study investigates G proteins more closely in this peripheral nerve plexus after chronic exposure to addictive drugs of the opiate and nonopiate type. After 6 days of treatment with either the mu receptor ligand fentanyl, the kappa- agonist U-50,488H or the alpha-2 adrenergic receptor ligand clonidine, at doses which render the myenteric plexus tolerant and dependent, the G protein subunits Go alpha and G beta were quantified by immunoblot analysis by using polyclonal antisera. Regardless of the drug used, these G proteins were found to be significantly increased in particulate membrane preparations linked to nerve somata and nerve terminals. This increase in G protein subunits is developed maximally after 6 days, is dose- dependent and reversible upon termination of the drug supply. The concentrations found elevated return to control levels within 4 to 5 days after commencing withdrawal. The common increase of Go alpha and G beta subunits observed after chronic opiate or clonidine exposure is associated with the phenomenon of cross-dependence among all drugs studied. The findings may suggest that in the guinea pig myenteric plexus multiple inhibitory receptor types make use of a common pool of G proteins.

Volume 258, Issue 3, pp. 790-796, 09/01/1991
Copyright © 1991 by American Society for Pharmacology and Experimental Therapeutics

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