Grosman N, Jensen S M, Johansen F F
Agents Actions. 1982 Oct;12(4):417-24. doi: 10.1007/BF01965920.
The stereospecificity of the action of opiates on rat mast cells was investigated by means of the l- and d-isomers levorphanol and dextrorphan. The dose-response curves for histamine release induced by the 2 drugs were of a similar shape with a maximum at 2 X 10(-3) M and a pronounced minimum at 5 X 10(-3) M. At concentrations below 5 X 10(-3) M the effect of both drugs resembled that of morphine, i.e. the release occurred rapidly and inhibition was observed with naloxone, codeine, and antimycin A. Levorphanol, dextrorphan, and the antagonist levallorphan at concentrations above 5 X 10(-3) M seemed to be toxic to mast cells. The uptake of 45Ca in connection with histamine release induced by pethidine, levorphanol, and dextrorphan was lower than that of control cells, whereas the uptake induced by morphine did not differ from that of controls. The inhibition of compound 48/80-induced histamine release by morphine was paralleled by a reduced 45Ca uptake. The time course for the inhibitory effect of preincubation with morphine was similar for the histamine released induced by morphine and by compound 48/80. Washing of the cells after preincubation with morphine was without effect on the inhibition of morphine-induced histamine release, whereas the inhibition of compound 48/80 was reduced. The present observation with morphine and compound 48/80 support our previous impression of similarities in their mode of action, but a mechanism implying an interference by morphine with the disposition of calcium could also account for the findings. The observed antagonism between morphine and calcium resembles that of opiate receptors, but histamine release induced by opiates does not involve stereospecific opiate receptors.
通过左旋吗啡和右旋吗啡的左旋体和右旋体异构体研究了阿片类药物对大鼠肥大细胞作用的立体特异性。两种药物诱导组胺释放的剂量 - 反应曲线形状相似，在2×10（-3）M时达到最大值，在5×10（-3）M时出现明显最小值。在浓度低于5×10（-3）M时，两种药物的作用类似于吗啡，即释放迅速发生，并且观察到纳洛酮、可待因和抗霉素A有抑制作用。左旋吗啡、右旋吗啡和拮抗剂左洛啡烷在浓度高于5×10（-3）M时似乎对肥大细胞有毒性。与哌替啶、左旋吗啡和右旋吗啡诱导的组胺释放相关的45Ca摄取低于对照细胞，而吗啡诱导的摄取与对照无差异。吗啡对化合物48/80诱导的组胺释放的抑制作用与45Ca摄取减少平行。吗啡预孵育的抑制作用的时间进程对于吗啡和化合物48/80诱导释放的组胺是相似的。用吗啡预孵育细胞后洗涤对吗啡诱导的组胺释放的抑制没有影响，而对化合物48/80的抑制作用减弱。目前关于吗啡和化合物48/80的观察结果支持我们之前对它们作用方式相似性的印象，但一种暗示吗啡干扰钙分布的机制也可以解释这些发现。观察到的吗啡和钙之间的拮抗作用类似于阿片受体的拮抗作用，但阿片类药物诱导的组胺释放不涉及立体特异性阿片受体。
