OPIOID RECEPTOR PROBES

具有Delta阿片拮抗剂的五肽脑啡肽类似物 活性将被各种亲电取代物修饰 Phe4残基以开发选择性或 以一种非平衡的方式特异性地阻断Delta受体。这些 配体将在体外对小鼠输精管和豚鼠进行测试。 回肠准备以评价选择性和非均衡性 效果的性质。将进行受体结合研究，以获得 额外支持共价键连接到三角洲位置。为了 评估和改进吗啡耐受性的模型，结合 MU特异性非平衡拮抗剂[~3H]β-FNA对大鼠脑片的作用 幼稚和宽容的小鼠将被调查。

Pentapeptide enkephalin analogues that possess delta opioid antagonist activity will be modified with a variety of electrophilic substitutents at the Phe4 residue in order to develop ligands that selectively or specifically block delta receptors in a nonequilibrium fashion. These ligands will be tested in vitro on the mouse vas deferens and guinea pig ileum preparations in order to evaluate the selectivity and nonequilibrium nature of the effect. Receptor binding studies will be conducted to obtain additional support for covalent bonding to delta sites. In order to evaluate and refine a model for morphine tolerance, the binding of the mu-specific nonequilibrium antagonist, [3H]Beta-FNA, to brain slices from naive and tolerant mice will be investigated.