Kosterlitz H W, Paterson S J
Philos Trans R Soc Lond B Biol Sci. 1985 Feb 19;308(1136):291-7. doi: 10.1098/rstb.1985.0029.
The endogenous opioid peptides are derived from three large precursors. Pro-opiocortin and proenkephalin yield [Met]enkephalin, carboxy-extended [Met]enkephalins and [Leu]enkephalin. The fragments of prodynorphin are all carboxy-extended [Leu]enkephalins. Three approaches are of importance for an analysis of the physiological functions of the different endogenous opioid peptides. First, since these peptides interact with more than one of the mu-, delta- and kappa-binding sites and thus with their receptors, it is necessary to synthesize peptides or non-peptides, which bind to only one of the sites. As far as narcotic analgesics are concerned, morphine fulfils these conditions since it interacts almost exclusively with the mu-receptor. Secondly, antagonists are required that are selective for only one of the opioid receptors, even when used in high concentrations. Finally, it is important to find circumscribed areas in the nervous system that possess only one type of opioid receptor. It is now known that in the rabbit cerebellum the opioid receptors are almost exclusively of the mu-type whereas in the guinea-pig cerebellum they are almost exclusively of the kappa-type.
内源性阿片肽源自三种大的前体。阿片促皮质素原和脑啡肽原产生甲硫氨酸脑啡肽、羧基端延长的甲硫氨酸脑啡肽和亮氨酸脑啡肽。强啡肽原的片段均为羧基端延长的亮氨酸脑啡肽。有三种方法对于分析不同内源性阿片肽的生理功能很重要。首先，由于这些肽与μ、δ和κ结合位点中的不止一种相互作用，从而与它们的受体相互作用，因此有必要合成仅与其中一个位点结合的肽或非肽。就麻醉性镇痛药而言，吗啡符合这些条件，因为它几乎只与μ受体相互作用。其次，需要仅对一种阿片受体具有选择性的拮抗剂，即使在高浓度使用时也是如此。最后，重要的是在神经系统中找到仅具有一种阿片受体类型的特定区域。现在已知在兔小脑中，阿片受体几乎全是μ型，而在豚鼠小脑中，它们几乎全是κ型。
