Meunier J, Mouledous L, Topham C M
Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, 205 route de Narbonne, 31077 cédex 4, Toulouse, France.
Peptides. 2000 Jul;21(7):893-900. doi: 10.1016/s0196-9781(00)00225-4.
Nociceptin and the ORL1 receptor share high sequence similarity with opioid peptides, particularly dynorphin A, and their receptors. However, nociceptin and dynorphin A may use distinct molecular pathways to bind and activate their cognate receptors. Activation of the kappa-opioid receptor by dynorphin A is thought to require interactions of its N-terminal hydrophobic domain (Y(1)GGF) with the receptor opioid binding pocket, located within the transmembrane helix bundle, while activation of the ORL1 receptor appears to require interactions of the positively charged core (R(8)KSARK) of nociceptin with the negatively charged second extracellular receptor loop.
痛敏肽和孤啡肽受体1（ORL1受体）与阿片肽，尤其是强啡肽A及其受体具有高度的序列相似性。然而，痛敏肽和强啡肽A可能通过不同的分子途径来结合并激活它们各自的受体。强啡肽A对κ-阿片受体的激活被认为需要其N端疏水结构域（Y(1)GGF）与位于跨膜螺旋束内的受体阿片结合口袋相互作用，而ORL1受体的激活似乎需要痛敏肽带正电荷的核心区域（R(8)KSARK）与带负电荷的受体第二胞外环相互作用。
