125I-FK 33-824: a selective probe for radioautographic labeling of mu opioid receptors in the brain

Abstract

The selectivity of the Met-enkephalin analog FK 33-824 (FK) for mu opioid receptors has been, over the years, a matter of controversy. We report here pharmacological and radioautographic data demonstrating that at nanomolar concentrations. 125I-FK interacts exclusively with mu sites. (1) Specific binding of 125I-FK to rat striatal membranes is totally inhibited by mu- and/or delta-preferring ligands according to monovalent, Michaelian kinetics, with a potency proportional to the affinity of competing drugs for mu receptors. (2) Unlabeled FK competes only at high concentration with the delta-selective ligand 3H-DPLPE and according to the same kinetics as the mu-selective agonist DAGO. (3) 125I-FK generates the same regional radioautographic labeling pattern as 3H-DAGO. We conclude that when used at nanomolar concentrations 125I-FK constitutes a selective probe for the radioautographic detection of mu opioid receptors at both light and electron microscopic levels.