Regulation of G proteins by chronic opiate and clonidine treatment in the guinea pig myenteric plexus
Ammer, H.; Nice, L.; Lang, J.; Schulz, R.
Journal of Pharmacology and Experimental Therapeutics 258(3): 790-796
1991
ISSN/ISBN: 0022-3565 PMID: 1679848 Document Number: 369928
G proteins have been implicated in the development of opioid dependence of the guinea pig myenteric plexus as chronic fentanyl elevates Go/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. The 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 common pool of G proteins.