OPIOID RECEPTOR RESERVE IN NORMAL AND MORPHINE-TOLERANT GUINEA-PIG ILEUM MYENTERIC PLEXUS
OPIOID RECEPTOR RESERVE IN NORMAL AND MORPHINE-TOLERANT GUINEA-PIG ILEUM MYENTERIC PLEXUS
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DOI：
10.1073/pnas.81.22.7253
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发表时间：
1984-01-01
期刊：
影响因子：
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通讯作者：
GOLDSTEIN, A
中科院分区：
文献类型：
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作者：
CHAVKIN, C;GOLDSTEIN, A
用定位烷基化剂-氯那曲胺测定豚鼠回肠肌丛中阿片受体的储备。用低浓度（< 10 nM）的。氯那曲胺引起正吗啡和啡肽a -的对数浓度-反应曲线平行移位（1-13）。对所得曲线的分析表明，Kd值为1.5 +-。0.5的同学们。10-6和10 +-。4同学。分别为9。用纳洛酮来区分。和.kappa。在此组织中，我们发现正吗啡和啡肽A-(1-13)的受体选择性在最大平行位移后没有变化，从而表明两者都有备用的。还有卡帕。受体存在。两种受体类型的备用受体比例均在90%左右。在吗啡耐受制剂（慢性颗粒植入）中，有明显的减少。受体对去甲吗啡的明显亲和力没有变化。备用受体部分的减少并不一定意味着结合位点数量的减少。受体储备的减少可能是阿片耐受性的基础，因为产生给定效果所需的激动剂浓度预计会随着受体储备的减少而增加。
The opioid receptor reserve was measured in the guinea pig ileum myenteric plexus by the site-directed alkylating agent, .beta.-chlornaltrexamine. Treatment of the tissue with low (< 10 nM) concentrations of .beta.-chlornaltrexamine caused a parallel shift of the log concentration-response curves for both normorphine and dynorphin A-(1-13). Analysis of the resulting curves indicated that the Kd values were 1.5 .+-. 0.5 .times. 10-6 and 10 .+-. 4 .times. 10-9, respectively. Using the naloxone Ke to distinguish between the .mu. and .kappa. receptors in this tissue, it was found that the receptor selectivities of normorphine and dynorphin A-(1-13) were unchanged after a maximum parallel shift, thus demonstrating that there are both spare .mu. and spare .kappa. receptors present. The spare-receptor fraction for both receptor types was about 90%. In morphine-tolerant preparations (chronic pellet implantation), there was an apparent reduction in the fraction of spare .mu. receptors without any change in the apparent affinity of normorphine. Reduction in the spare receptor fraction does not necessarily imply reduction in the number of binding sites. This reduction in receptor reserve is probably the basis of opioid tolerance, since the agonist concentration needed to produce a given effect is expected to increase as the receptor reserve decreases.