Verspohl E J, Berger U, Ammon H P
Biochim Biophys Acta. 1986 Sep 19;888(2):217-24. doi: 10.1016/0167-4889(86)90024-8.
The binding and the insulinotropic effects of enkephalin analogs and of morphine were investigated in rat pancreatic islets. Binding of [3H]Met-enkephalin was saturable, specific and reversible; the rank order for inhibition competition of [3H]Met-enkephalin binding by various compounds was Met-enkephalin = D-Ala2-MePhe4, Met(0)ol enkephalin) greater than Leu-enkephalin greater than morphine with half-maximal inhibitory constants (IC50) of approx. 0.3, 0.3, 100 and greater than 100 nM, respectively. Both the natural enkephalins exerted their insulinotropic effect only at stimulatory glucose concentrations. They had a dual action; whereas insulin secretion was increased at low enkephalin concentration, this effect was reversed at higher concentrations. However, the various enkephalins exerted this effect at different concentrations; only the EC50 values (half-maximal effective concentrations) of their insulinotropic effect were in the same range as the IC50 values of inhibition of [3H]met-enkephalin binding. Cysteamine pretreatment of rats (depletion of somatostatin containing D-cells and decrease in somatostatin secretion) did not change the Met-enkephalin effect on insulin secretion. In contrast to Met-enkephalin, binding of [3H]morphine to islets was not saturable, and morphine had no effect on insulin secretion unless at unphysiologically high concentrations. The data, therefore, indicate that: mu-receptors (affinity for morphine) do not play a role in rat pancreatic islets; delta-receptors (binding site for Met-enkephalin when mu-receptors are not present) mediate the insulinotropic effect of low Met-enkephalin concentrations; and the insulinotropic action of Met-enkephalin is not mediated indirectly via the paracrine effect of an inhibition of somatostatin secretion.
在大鼠胰岛中研究了脑啡肽类似物和吗啡的结合及促胰岛素分泌作用。[3H]甲硫氨酸脑啡肽的结合具有饱和性、特异性和可逆性；各种化合物对[3H]甲硫氨酸脑啡肽结合的抑制竞争顺序为甲硫氨酸脑啡肽 = D - 丙氨酸2 - 甲基苯丙氨酸4，甲硫氨酸(0)脑啡肽大于亮氨酸脑啡肽大于吗啡，其半数最大抑制常数(IC50)分别约为0.3、0.3、100和大于100 nM。两种天然脑啡肽仅在刺激葡萄糖浓度时发挥促胰岛素分泌作用。它们具有双重作用；在低脑啡肽浓度时胰岛素分泌增加，而在较高浓度时这种作用则相反。然而，各种脑啡肽在不同浓度时发挥这种作用；仅其促胰岛素分泌作用的EC50值（半数最大有效浓度）与抑制[3H]甲硫氨酸脑啡肽结合的IC50值在同一范围内。用半胱胺预处理大鼠（减少含生长抑素的D细胞并降低生长抑素分泌）并未改变甲硫氨酸脑啡肽对胰岛素分泌的作用。与甲硫氨酸脑啡肽相反，[3H]吗啡与胰岛的结合不饱和，并且吗啡对胰岛素分泌无作用，除非在非生理的高浓度时。因此，数据表明：μ受体（对吗啡的亲和力）在大鼠胰岛中不起作用；δ受体（在不存在μ受体时甲硫氨酸脑啡肽的结合位点）介导低浓度甲硫氨酸脑啡肽的促胰岛素分泌作用；并且甲硫氨酸脑啡肽的促胰岛素分泌作用不是通过抑制生长抑素分泌的旁分泌效应间接介导的。
