Abstract

A site-directed alkylating agent was used to inactivate one or more types of opioid receptor in two bioassay preparations in the presence of type-selective ligands as protectors of other opioid receptor types. Since the pharmacological potency of an agonist is decreased when the receptor type through which it acts has been inactivated, the method can be used to characterize the pharmacological selectivity of opioid agonists. All of the smaller opioid products of the enkephalin gene were found to be delta-selective in the mouse vas deferens, but BAM-12P, BAM- 22P , and Peptide E were not. In the same tissue, beta c-endorphin was not mu-selective, but in the guinea pig ileum preparation it evidently combined with mu and kappa receptors. The presence of functional epsilon receptors, however, could not be ruled out. The approach described here is applicable to any pharmacologically active receptors of which there are multiple types, and for which site-directed alkylating agents and type-selective protector ligands are available.