PHARMACOLOGICAL CHARACTERIZATION OF THE CLONED KAPPA-OPIOID, DELTA-OPIOID, AND MU-OPIOID RECEPTORS

Opioid drugs, such as morphine, and the endogenous opioid peptides, namely the enkephalins, endorphins, and dynorphins, exert a wide spectrum of physiological and behavioral effects, including effects on pain perception, mood, motor control, and autonomic functions. These effects are mediated via membrane-bound receptors, of which the best characterized are the kappa, delta, and mu receptors. The existence of these distinct types of opioid receptors has recently been confirmed by molecular cloning. In the present study, we have examined the pharmacological profiles of the cloned kappa, delta, and mu receptors using a battery of widely employed opioid agents. Our results suggest that the cloned kappa and mu receptors have pharmacological characteristics similar to those of the endogenously expressed kappa(1) and mu receptors, respectively. The cloned delta receptor displays a pharmacological profile consistent with that of a delta(2) receptor. Opioid agents with abuse potential possess high affinities for the mu receptor. The availability of the cloned receptors will facilitate the identification and development of more specific and selective compounds with greater therapeutic potential and fewer undesirable side effects.