Abstract

Treatment of NG108-15 cells with 1 nM or 10 nM etorphine for 24 hr produced an identical magnitude of compensatory increase in prostaglandin E1-stimulated adenylate cyclase activity. Activity of etorphine was retained, albeit reduced, in NG108-15 cells treated with 1 nM etorphine but not in cells treated with 10 nM etorphine. Exposure to 100 microM morphine for 72 hr produced a complete loss of morphine and levorphanol but not Leu5-enkephalin activity in NG108-15 hybrid cells. Apparently, the loss of opiate activity involves a multiple-step process. Short-term incubation with 10 nM etorphine (less than 3 hr) produced loss of opiate activity with minimal alteration in [3H]diprenorphine specific binding. Long-term exposure to 10 nM etorphine (greater than or equal to 24 hr) produced down-regulation of the receptor. A mechanism similar to that of beta-adrenergic receptor desensitization may be involved in opiate receptor desensitization in NG108-15 cells.