Davies J, Dray A
Br J Pharmacol. 1978 May;63(1):87-96. doi: 10.1111/j.1476-5381.1978.tb07778.x.
1 The actions of morphine, methionine and leucine enkephalin, administered electrophoretically, were studied on supraspinal neurones in the cortex and brainstem of the rat anaesthetized with urethane and on spinal Renshaw cells and dorsal horn interneurones in the cat anaesthetized with pentobarbitone.2 The majority of Renshaw cells and cortical and brainstem neurones were excited by all three compounds although some supraspinal neurones were depressed.3 Naloxone reversibly antagonized both excitatory and depressant actions of morphine and enkephalin. Acetylcholine-induced excitation but not amino acid-induced excitation was also antagonized by naloxone.4 Neither morphine nor the enkephalins had any naloxone-reversible action on dorsal horn neurones when ejected from conventional multibarrelled electrodes. However, morphine but not enkephalin, administered into the substantia gelatinosa region of the spinal cord selectively reduced responses to noxious stimuli of neurones in deeper laminae. Naloxone administered into the same region antagonized this action of morphine.5 Intravenous morphine also antagonized responses of dorsal horn neurones to noxious stimuli and subsequent intravenous naloxone reversed this effect.6 It was concluded that the excitatory and inhibitory effects of morphine and enkephalin on central neurones may be mediated by actions on different opiate receptors and that depression of noxious responses of dorsal horn neurones may be relevant to the analgesic action of morphine.
研究了通过电泳给予吗啡、甲硫氨酸脑啡肽和亮氨酸脑啡肽对用乌拉坦麻醉的大鼠皮质和脑干中的脊髓上神经元以及用戊巴比妥麻醉的猫的脊髓闰绍细胞和背角中间神经元的作用。
大多数闰绍细胞以及皮质和脑干神经元受到这三种化合物的兴奋,尽管一些脊髓上神经元受到抑制。
纳洛酮可逆地拮抗吗啡和脑啡肽的兴奋和抑制作用。纳洛酮也拮抗乙酰胆碱诱导的兴奋,但不拮抗氨基酸诱导的兴奋。
当从传统的多管电极喷射时,吗啡和脑啡肽对背角神经元均没有任何纳洛酮可逆作用。然而,将吗啡而非脑啡肽注入脊髓胶状质区域可选择性降低深层板层神经元对有害刺激的反应。将纳洛酮注入同一区域可拮抗吗啡的这一作用。
静脉注射吗啡也拮抗背角神经元对有害刺激的反应,随后静脉注射纳洛酮可逆转这一效应。
得出的结论是,吗啡和脑啡肽对中枢神经元的兴奋和抑制作用可能是通过作用于不同的阿片受体介导的,并且背角神经元有害反应的抑制可能与吗啡的镇痛作用有关。