Malfacini Davide, Caló Girolamo
Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany.
Section of Pharmacology, Department of Medical Sciences, National Institute of Neurosciences, University of Ferrara, Ferrara, Italy.
Handb Exp Pharmacol. 2019;254:69-89. doi: 10.1007/164_2018_200.
The nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) is a G protein-coupled receptor involved in the regulation of several physiological functions and pathological conditions. Thus, researchers from academia and industry are pursuing NOP to discover and study novel pharmacological entities. In a multidisciplinary effort of pharmacologists, medicinal chemists, and molecular and structural biologists the mechanisms of NOP activation and inhibition have been, at least partially, disentangled. Here, we review the in vitro methodologies employed, which have contributed to our understanding of this target. We hope this chapter guides the reader through the mostly established assay platforms to investigate NOP pharmacology, and gives some hints taking advantage from what has already illuminated the function of other GPCRs. We analyzed the pharmacological results obtained with a large panel of NOP ligands investigated in several assays including receptor binding, stimulation of GTPγS binding, decrease of cAMP levels, calcium flux stimulation via chimeric G proteins, NOP/G protein and NOP/β-arrestin interaction, label-free assays such as dynamic mass redistribution, and bioassays such as the electrically stimulated mouse vas deferens.
痛敏肽/孤啡肽FQ（N/OFQ）肽受体（NOP）是一种G蛋白偶联受体，参与多种生理功能和病理状态的调节。因此，来自学术界和工业界的研究人员都在研究NOP，以发现和研究新型药理活性物质。通过药理学家、药物化学家以及分子和结构生物学家的多学科努力，NOP激活和抑制的机制至少已部分得到阐明。在此，我们综述了所采用的体外方法，这些方法有助于我们对该靶点的理解。我们希望本章能引导读者了解用于研究NOP药理学的大多数已确立的检测平台，并从已阐明其他G蛋白偶联受体功能的研究中给出一些提示。我们分析了在多种检测中使用大量NOP配体所获得的药理学结果，这些检测包括受体结合、GTPγS结合刺激、cAMP水平降低、通过嵌合G蛋白刺激钙通量、NOP/G蛋白和NOP/β-抑制蛋白相互作用、无标记检测如动态质量再分布以及生物检测如电刺激小鼠输精管。
