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

The efficacies of different κ agonists to activate κ opioid receptor (κOR) and to induce acute homologous desensitization of κOR-mediated extracellular acidification response (ECAR) have been investigated using microphysiometry in Chinese hamster ovary (CHO) cells stably expressing κOR. Although efficacy of dynorphin A (DA) to stimulate κOR-mediated ECAR was comparable to that of U69593, DA displayed a significant higher efficacy to induce desensitization of κOR. Moreover, the half life for the recovery of κOR 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 μ opioid receptors (μOR) stably expressed in CHO cells were comparable to those of other μ agonists.