A subclassification of multiple opiate receptors by means of selective tolerance development

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.