Morphine-Induced mu-opioid receptor desensitization.
Morphine has been widely accepted as the opioid agonist that sustains signaling because it does not cause receptor desensitization or internalization. This notion has led to the hypothesis that long-term morphine treatment initiates downstream adaptations that underlie tolerance and dependence. This study uses whole-cell recordings from neurons in the locus ceruleus to measure the potassium current induced by morphine. The results show that morphine does cause short-term desensitization. The desensitization induced by morphine was slower and smaller then that induced by [MET](5)-enkephalin (ME). After a brief application of a saturating concentration of ME, the current induced by morphine was smaller, and desensitization was not observed. In tissue taken from morphine-treated animals, the peak current induced by morphine was the same as in untreated animals, but morphine-induced desensitization was facilitated. The results suggest that morphine, like other agonists, can initiate receptor desensitization to decrease signaling.
Dang
Vu C
VC
Vollum Institute, Oregon Health Sciences University, Portland, OR 97239, USA.
Williams
John T
JT
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*
D000701:Analgesics, Opioid; D015221:Potassium Channels; D017450:Receptors, Opioid, mu; D009020:Morphine