Effects of NMDA receptor antagonists on delta1- and delta2-opioid receptor agonists-induced changes in the mouse brain [3H]DPDPE binding.
Effects of NMDA receptor antagonists on delta1- and delta2-opioid receptor agonists-induced changes in the mouse brain [3H]DPDPE binding.
复制标题
NMDA 受体拮抗剂对 delta1- 和 delta2-阿片受体激动剂诱导的小鼠大脑 [3H]DPDPE 结合变化的影响。
DOI：
10.1016/s0014-2999(97)01216-8
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发表时间：
1997
影响因子：
5
通讯作者：
Bhargava,HN
中科院分区：
文献类型：
--
作者：
Cao,YJ;Bian,JT;Bhargava,HN
将雄性Swiss-Webster小鼠脑室内（i. c. v.）用[d-Pen 2，d-Pen 5]脑啡肽（20 μg/小鼠）每天两次，持续2天。该程序导致[3 H][d-Pen 2，d-Pen 5]脑啡肽结合位点下调，Bmax值降低52%。每日两次注射（+）-5-甲基-10，11-二氢-5H-二苯并-[a，d]-环庚烯-5，10-亚胺（MK-801）（0.1 mg/kg，i. p.）或[（−）3-SR，4a-RS，8a-SR-6-（膦酰基甲基）-1，2，3，4，4a，5，6，7，8，8a-十氢异喹啉-3-羧酸]（LY 235959）（2 mg/kg，i. p.），N-甲基-d-天冬氨酸（NMDA）受体的非竞争性和竞争性拮抗剂分别作用2天，不改变[~ 3 H][d-Pen 2，d-Pen 5]脑啡肽与小鼠脑结合的Bmax或Kd值。MK-801与[d-Pen 2，d-Pen 5]脑啡肽同时给药可逆转[3 H][d-Pen 2，d-Pen 5]脑啡肽的Bmax值降低，但LY 235959与[d-Pen 2，d-Pen 5]脑啡肽不同时给药。每天两次注射[d-Ala 2，Glu 4] deltorphin II（20 μg/只），连续2天，可引起[~ 3 H][d-Pen 2，d-Pen 5]脑啡肽与脑细胞膜结合的Kd值增加，但Bmax值不增加。[d-Ala 2，Glu 4]deltorphin II与LY 235959同时给药可逆转多次注射[d-Ala 2，Glu 4]deltorphin II诱导的[3 H][d-Pen 2，d-Pen 5]脑啡肽结合Kd值升高，但MK-801无影响。结果提示，多次注射δ1和δ2阿片受体激动剂可通过改变[~ 3 H][d-Pen 2，d-Pen 5]脑啡肽结合的Bmax和Kd值，下调脑内δ1阿片受体。MK-801和LY 235959分别逆转δ1-和δ2-阿片受体激动剂诱导的脑δ1-阿片受体下调，其机制明显不同。得出结论，δ1-阿片受体激动剂短期给药可通过降低配体的Bmax下调脑δ1-阿片受体，MK-801同时给药可部分逆转该结果，但LY 235959未逆转该结果。另一方面，δ2-阿片受体激动剂短期给药可通过增加配体的Kd下调脑δ1-阿片受体，LY 235959联合给药可部分逆转该结果，但MK-801不能逆转该结果。
Male Swiss-Webster mice were injected intracerebroventricularly (i.c.v.) with [d-Pen2,d-Pen5]enkephalin (20 μg/mouse) twice a day for 2 days. This procedure resulted in down-regulation of binding sites for [3H ][d-Pen2,d-Pen5]enkephalin as evidenced by a 52% decrease in the Bmaxvalue. Twice daily injections of (+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]-cyclohepten-5,10-imine (MK-801) (0.1 mg/kg, i.p.) or [(−)3-SR,4a-RS,8a-SR-6-(phosphonomethyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid] (LY 235959) (2 mg/kg, i.p.), the noncompetitive and competitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, respectively, for 2 days did not alter the Bmaxor Kdvalue of [3H ][d-Pen2,d-Pen5]enkephalin binding to the mouse brain. Concurrent treatment of MK-801, but not of LY 235959 with [d-Pen2,d-Pen5]enkephalin, reversed the decreases in Bmaxvalue of [3H ][d-Pen2,d-Pen5]enkephalin. Twice daily injections of [d-Ala2,Glu4] deltorphin II (20 μg/mouse) for 2 days caused an increase in the Kdvalue, but not the Bmaxvalue of [3H ][d-Pen2,d-Pen5]enkephalin to bind to brain membranes. Concurrent treatment of [d-Ala2,Glu4]deltorphin II with LY 235959 reversed the increase in Kdvalue of [3H ][d-Pen2,d-Pen5]enkephalin binding induced by multiple injections of [d-Ala2,Glu4]deltorphin II, but MK-801 had no effect. The results suggest that multiple injections of δ1- and δ2-opioid receptor agonists down-regulate δ1-opioid receptors of the brain by modifying Bmaxand Kdvalues of [3H ][d-Pen2,d-Pen5]enkephalin binding, respectively. MK-801 and LY 235959 reverse δ1- and δ2-opioid receptor agonists-induced down-regulation of brain δ1-opioid receptor, respectively, apparently by different mechanisms. It is concluded that short term treatment of mice with δ1-opioid receptor agonist down-regulates brain δ1-opioid receptors by decreasing Bmaxof the ligand which is partially reversed by concurrent treatment with MK-801 but not by LY 235959. On the other hand, short term treatment of mice with δ2-opioid receptor agonist down-regulates brain δ1-opioid receptors by increasing Kdof the ligand which is partially reversed by concurrent treatment with LY 235959 but not by MK-801.