金仓鼠脑内的 kappa 受体

目的：研究〔３Ｈ〕依托啡与金仓鼠脑内ｋａｐｐａ受体结合及其在脑内分布的特性。方法：用受体结合和药物的竞争抑制试验研究〔３Ｈ〕依托啡与金仓鼠脑匀浆中ｋａｐｐａ受体结合。结果：〔３Ｈ〕依托啡与金仓鼠脑匀浆中ｋａｐｐａ受体结合的Ｋｄ值和Ｂｍａｘ值分别为０．５２ｎｍｏｌ·Ｌ－１和３４．０ｐｍｏｌ·ｇ－１蛋白。５μｍｏｌ·Ｌ－１（Ｄ－Ａｌａ２，Ｄ－Ｌｅｕ５）脑啡肽可完全阻断〔３Ｈ〕依托啡与ｋａｐｐａ受体的结合。该结合易被苯吗啡烷类及奥列巴文类药物取代，而不易被强啡肽Ａ（１－１３）取代。金仓鼠脑内ｋａｐｐａ受体存在不同的局部分布，纹状体和中脑的密度较高（Ｋｄ和Ｂｍａｘ值为０．４８±０．０２１ｎｍｏｌ·Ｌ－１和２６．６±２．１ｐｍｏｌ·ｇ－１蛋白；０．４１±０．０１５ｎｍｏｌ·Ｌ－１和２４．９±０．３６ｐｍｏｌ·ｇ－１蛋白），大脑皮层的密度较低（Ｋｄ和Ｂｍａｘ值为０．４２±０．０２ｎｍｏｌ·Ｌ－１和１０．５±０．８５ｐｍｏｌ·ｇ－１蛋白）。结论：金仓鼠脑内有优势的ｋａｐｐａ受体，它不同于经典的ｋａｐｐａ受体，可能属于ｋａｐ－ｐａ２受体。纹状体和中脑的ｋａｐｐａ受体分布密度最高。

Kappa receptor in gloden hamster

Aim:The feature of kappa receptor binding and distribution of 3H etorphine in golden hamster brain was studied. Methods: The kappa receptor binding of 3H etorphine in golden hamster brain was carried out with binding assay and competition binding. Results: after blockade of mu and delta receptors by unlabelled 30 nmol·L -1 morphine and 100 nmol·L -1 DADLE, 3H etorphine was still able to bind to residual sites with high affinity. Scatchard analysis showed that K d and B max were 0 52 nmol·L -1 and 34 0 pmol·g -1 protein for the kappa binding of 3H etorphine to whole brain homogenates respectively. The specific binding was completely abolished by 5 μmol·L -1 DADLE, suggesting that 3H etorphine did not bind to DADLE insensitive sites which correspond to the kappa 1 receptors. Competition binding studies indicated that benzomorphan and oripavine drugs showed high affinity to the kappa receptors whereas dynorphin A(1 13) did not. These results suggest that the kappa receptors which interacted with 3H etorphine differ form typical kappa receptors, Possibly belong to kappa 2 receptors. The kappa receptor existed different regional distribution in golden haster brain. Their K d and B max were 0 48±0 021 nmol·L -1 and 26 6±2 1 pmol·g -1 protein in corpus callosum, 0 41±0 015 nmol·L -1 and 24 9±0 36 pmol·g -1 protein in mid brain, and 0 42±0 02 nmol·L -1 and 10 5±0 85 pmol·g -1 protein in cerebral cortex respectively. Conclusion: The brain of golden hamster contains mainly kappa receptors, which differ from typical kappa receptors, possibly belong to kappa 2 receptors. The distribution of the kappa receptors is highest in corpus callosum and mid brain.