Mansour A, Hoversten M T, Taylor L P, Watson S J, Akil H
Mental Health Research Institute, University of Michigan, Ann Arbor 48109-0720, USA.
Brain Res. 1995 Nov 27;700(1-2):89-98. doi: 10.1016/0006-8993(95)00928-j.
The opioid peptides are derived from three prohormone precursors referred to as proopiomelanocortin (POMC), proenkephalin (ProEnk) and prodynorphin (ProDyn). Following specific cleavage, several biologically active peptides are generated that can bind to the mu, delta and kappa receptors. The present study examines the receptor binding affinities of the POMC, ProEnk and ProDyn peptides to the cloned mu, delta and kappa receptors expressed transiently in transfected COS-1 cells. Consistent with previous findings using brain homogenates, competition studies demonstrate that no opioid peptide family can be exclusively associated with a specific opioid receptor type. Short ProEnk peptides, such as Leu- and Met-enkephalin are selective for delta, but C-terminally extended peptides such as Met-Enk-Arg-Gly-Leu and Met-Enk-Arg-Phe have a high affinity to micro, delta and kappa. Similarly, Peptide E, the BAM peptides, and metorphamide have a high affinity for all three opioid receptor types. While dynorphin A peptides and alpha- and beta-neoendorphin have a preference for kappa, they also bind the cloned delta and mu receptors. Our findings do not easily fit a simple 'message-address' model where the Try-Gly-Gly-Phe core is extended and this gradually alters selectivity. Rather, the pattern appears more discontinuous, and would fit better with the idea of two similar but distinct cores; a Try-Gly-Gly-Phe Met- or Leu core that is necessary and sufficient for mu and delta but not kappa and a Tyr-Gly-Gly-Phe-Met or Leu core with an Arg-X extension that is equally necessary and sufficient for kappa.
阿片肽源自三种前激素前体，分别称为阿黑皮素原（POMC）、脑啡肽原（ProEnk）和强啡肽原（ProDyn）。经过特定的切割后，会产生几种具有生物活性的肽，它们可以与μ、δ和κ受体结合。本研究检测了POMC、ProEnk和ProDyn肽对在转染的COS-1细胞中瞬时表达的克隆μ、δ和κ受体的受体结合亲和力。与先前使用脑匀浆的研究结果一致，竞争研究表明，没有一个阿片肽家族能与特定的阿片受体类型完全相关。短的ProEnk肽，如亮氨酸脑啡肽和甲硫氨酸脑啡肽对δ受体具有选择性，但C末端延长的肽，如甲硫氨酸脑啡肽-精氨酸-甘氨酸-亮氨酸和甲硫氨酸脑啡肽-精氨酸-苯丙氨酸对μ、δ和κ受体具有高亲和力。同样，肽E、BAM肽和甲硫酰胺对所有三种阿片受体类型都具有高亲和力。虽然强啡肽A肽以及α和β-新内啡肽对κ受体有偏好，但它们也能结合克隆的δ和μ受体。我们的研究结果不容易符合一个简单的“信息-地址”模型，即酪氨酸-甘氨酸-甘氨酸-苯丙氨酸核心被延长，这逐渐改变了选择性。相反，这种模式似乎更不连续，更符合两个相似但不同的核心的概念；一个酪氨酸-甘氨酸-甘氨酸-苯丙氨酸-甲硫氨酸或亮氨酸核心，对μ和δ受体是必要且充分的，但对κ受体不是，以及一个带有精氨酸-X延伸的酪氨酸-甘氨酸-甘氨酸-苯丙氨酸-甲硫氨酸或亮氨酸核心，对κ受体同样是必要且充分的。
