Effects of aquaporin4 deficiency on opioid receptors characteristics in naive and chronic morphine-treated mice.
Our previous study indicated that aquaporin4 (AQP4) deficiency potentiated morphine analgesia, but attenuated tolerance and physical dependence induced by chronic exposure to morphine. However, the mechanisms remained to be explored. In the present study, effects of AQP4 deficiency on opioid receptor characteristics were investigated by [(3)H]-diprenorphine binding assays. In basal condition, the K(d) values of opioid receptors increased from 0.27+/-0.03 nM in wild-type mice to 0.44+/-0.04 nM in AQP4 deficient mice. Meanwhile, the density (B(max) values) of opioid receptors increased from 0.40+/-0.04 pmol/mg protein in wild-type mice to 0.66+/-0.04 pmol/mg protein in AQP4 deficient mice. After chronic morphine treatment, the affinity of opioid receptors decreased in wild-type mice, in which the K(d) value increased from 0.27+/-0.03 nM to 0.40+/-0.04 nM, while no change in the density of opioid receptors was observed. In AQP4 knockout mice, the effects of chronic morphine treatment on opioid receptors were similar to that in wild-type mice, in which the K(d) values increased from 0.44+/-0.04 nM to 0.64+/-0.08 nM, whereas the density had no significant change. Taken together, at the first time, we found that AQP4 deficiency decreased the affinity and increased the density of opioid receptors. Additionally, AQP4 deficiency did not affect chronic morphine-induced alterations of opioid receptor characteristics.
Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China.
Ji-Fang
JF
Wang
Zhi-Yuan
ZY
Wang
Ning
N
Wu
Hai-Tao
HT
Yan
Jin
J
Li
D000701:Analgesics, Opioid / Q000633:toxicity*; D000818:Animals; D051401:Aquaporin 4 / Q000172:deficiency* / Q000235:genetics; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004174:Diprenorphine / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000633:toxicity*; D011869:Radioligand Assay; D011957:Receptors, Opioid / Q000378:metabolism*; D014316:Tritium
D000701:Analgesics, Opioid; C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D011957:Receptors, Opioid; D014316:Tritium; D004174:Diprenorphine; D009020:Morphine