Studies of μ-, κ-, and δ-Opioid Receptor Density and G Protein Activation in the Cortex and Thalamus of Monkeys

该死的 化学 脑啡肽 μ-阿片受体 立体化学 结晶学 受体 兴奋剂 类阿片 生物化学
作者
Mei‐Chuan Ko,H. Lee,Charlotte Harrison,Mary J. Clark,Hyejin Song,Norah N. Naughton,J H Woods,JR Traynor
出处
期刊:Journal of Pharmacology and Experimental Therapeutics [American Society for Pharmacology and Experimental Therapeutics]
卷期号:306 (1): 179-186 被引量:45
标识
DOI:10.1124/jpet.103.050625
摘要

The aim of this study was to investigate the relative density of μ-, κ-, and δ-opioid receptors (MOR, KOR, and DOR) and guanosine 5′-O-(3-[35S]thio)triphosphate ([35S]GTPγS) binding stimulated by full agonists in cortical and thalamic membranes of monkeys. The binding parameters [Bmax (femtomoles per milligram)/Kd (nanomolar)] were as follows: [3H][d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) (MOR; 80/0.7), [3H]U69593 [(5α,7α,8β)-(–)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro(4,5)dec-8-yl) benzeneacetamide] (KOR; 116/1.3), and [3H][d-Pen2,d-Pen5]-enkephalin (DPDPE) (DOR; 87/1.3) in the cortex; [3H]DAMGO (147/0.9), [3H]U69593 (75/2.5), and [3H]DPDPE (22/2.0) in the thalamus. The relative proportions of MOR, KOR, and DOR in the cortex were 28, 41, and 31% and in the thalamus were 60, 31, and 9%. Full selective opioid agonists, DAMGO (EC50 = 532–565 nM) and U69593 (EC50 = 80–109 nM) stimulated [35S]GTPγS binding in membranes of cortex and thalamus, whereas SNC80 [(+)-4-[(αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethyl-benzamide] (DOR; EC50 = 68 nM) was only active in cortical membranes. The magnitudes of [35S]GTPγS binding stimulated by these agonists were similar in the cortex, ranging from 17 to 25% over basal binding. In the thalamus, DAMGO and U69593 increased [35S]GTPγS binding by 44 and 23% over basal, respectively. Opioid agonist-stimulated [35S]GTPγS binding was blocked selectively by antagonists for MOR, KOR, and DOR. The amount of G protein activated by agonists was highly proportional to the relative receptor densities in both regions. These results distinguish the ability of opioid agonists to activate G proteins and provide a functional correlate of ligand-binding experiments in the monkey brain. In particular, the relative densities of opioid receptor binding sites in the two brain areas reflect their functional roles in the pharmacological actions of opioids in the central nervous system of primates.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
4秒前
4秒前
情怀应助科研通管家采纳,获得10
4秒前
4秒前
乐乐应助科研通管家采纳,获得10
4秒前
热心乌完成签到,获得积分0
6秒前
ghy完成签到,获得积分10
6秒前
粥小周发布了新的文献求助10
6秒前
2568269431完成签到 ,获得积分10
12秒前
Hester完成签到,获得积分10
12秒前
罗实完成签到 ,获得积分10
13秒前
搞怪的紫雪完成签到,获得积分10
13秒前
ll发布了新的文献求助30
15秒前
迷人的沛山完成签到 ,获得积分10
15秒前
贾文斌完成签到,获得积分10
16秒前
17秒前
愤怒的之玉完成签到 ,获得积分10
19秒前
梁晓婉完成签到,获得积分10
19秒前
zdx1022完成签到,获得积分10
21秒前
xmz完成签到,获得积分10
23秒前
Haucicy完成签到 ,获得积分10
27秒前
落后的听双完成签到 ,获得积分10
31秒前
李健的小迷弟应助jackycas采纳,获得10
39秒前
1438132306完成签到 ,获得积分10
39秒前
正直的煎饼完成签到,获得积分10
48秒前
54秒前
Jane发布了新的文献求助10
58秒前
DUANYALI完成签到,获得积分10
1分钟前
王粒完成签到,获得积分10
1分钟前
1分钟前
1分钟前
zzz完成签到,获得积分10
1分钟前
knose完成签到,获得积分10
1分钟前
科目三应助自然代萱采纳,获得10
1分钟前
潇潇雨歇发布了新的文献求助10
1分钟前
诸葛烤鸭完成签到,获得积分10
1分钟前
skbkbe完成签到,获得积分10
1分钟前
pluto应助安详怀蕾采纳,获得10
1分钟前
1分钟前
霓娜酱完成签到 ,获得积分10
1分钟前
高分求助中
【此为提示信息,请勿应助】请按要求发布求助,避免被关 20000
Continuum Thermodynamics and Material Modelling 2000
Encyclopedia of Geology (2nd Edition) 2000
105th Edition CRC Handbook of Chemistry and Physics 1600
Maneuvering of a Damaged Navy Combatant 650
Периодизация спортивной тренировки. Общая теория и её практическое применение 310
Mixing the elements of mass customisation 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3779759
求助须知:如何正确求助?哪些是违规求助? 3325232
关于积分的说明 10221975
捐赠科研通 3040376
什么是DOI,文献DOI怎么找? 1668788
邀请新用户注册赠送积分活动 798775
科研通“疑难数据库(出版商)”最低求助积分说明 758549