A Subclassification of Multiple Opiate Receptors by Means of Selective Tolerance Development

Abstract

The chronic activation of opiate receptors results in the development of tolerance. On theoretical grounds, the appearance of cross-tolerance between different opioids should imply that these compounds exhibit an identical pattern on receptor activation. Tests with isolated tissue preparations, e.g. the guinea-pig ileum, made highly tolerant in vivo to the mu-agonist morphine proved that these were of almost unchanged sensitivity to different types of receptor agonists such as kappa-agonists. Thus, the ability to selectively induce tolerance on particular types of opiate receptors represents a reliable tool for the differentiation and characterization of multiple opiate receptors. Moreover, this technique facilitated the demonstration of subtypes of the already known opiate receptors.