DIFFERENTIAL EFFICACIES OF KAPPA-AGONIST TO INDUCE HOMOLOGOUS DESENSITIZATION OF HUMAN KAPPA-OPIOID RECEPTOR

The efficacies of different kappa agonists to activate kappa opioid re ceptor (kappa OR) and to induce acute homologous desensitization of ka ppa OR-mediated extracellular acidification response (ECAR) have been investigated using microphysiometry in Chinese hamster ovary (CHO) cel ls stably expressing kappa OR. Although efficacy of dynorphin A (DA) t o stimulate kappa OR-mediated ECAR was comparable to that of U69593, D A displayed a significant higher efficacy to induce desensitization of kappa OR. Moreover, the half life for the recovery of kappa OR respon siveness after DA prechallenge was four times longer than those observ ed after U69593 or etorphine pretreatment. in contrast, the efficacy o f DA to stimulate and desensitize mu opioid receptors (mu OR) stably e xpressed in CHO cells were comparable to those of other mu agonists. ( C) 1998 Elsevier Science Ireland Ltd.