Differential efficacies of κ agonists to induce homologous desensitization of human κ opioid receptor

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