Kukkonen Jyrki P
Biochemistry and Cell Biology, Department of Veterinary Biosciences, University of Helsinki, POB 66, FIN-00014, Helsinki, Finland.
Curr Top Behav Neurosci. 2017;33:17-50. doi: 10.1007/7854_2016_49.
Orexin/hypocretin peptide (orexin-A and orexin-B) signaling is believed to take place via the two G-protein-coupled receptors (GPCRs), named OX and OX orexin receptors, as described in the previous chapters. Signaling of orexin peptides has been investigated in diverse endogenously orexin receptor-expressing cells - mainly neurons but also other types of cells - and in recombinant cells expressing the receptors in a heterologous manner. Findings in the different systems are partially convergent but also indicate cellular background-specific signaling. The general picture suggests an inherently high degree of diversity in orexin receptor signaling.In the current chapter, I present orexin signaling on the cellular and molecular levels. Discussion of the connection to (potential) physiological orexin responses is only brief since these are in focus of other chapters in this book. The same goes for the post-synaptic signaling mechanisms, which are dealt with in Burdakov: Postsynaptic actions of orexin. The current chapter is organized according to the tissue type, starting from the central nervous system. Finally, receptor signaling pathways are discussed across tissues, cell types, and even species.
如前几章所述,食欲素/下丘脑泌素肽(食欲素-A和食欲素-B)信号传导被认为是通过两种G蛋白偶联受体(GPCRs)发生的,即OX1和OX2食欲素受体。食欲素肽的信号传导已在多种内源性表达食欲素受体的细胞中进行了研究——主要是神经元,但也包括其他类型的细胞——以及在以异源方式表达这些受体的重组细胞中进行了研究。不同系统中的研究结果部分是一致的,但也表明了细胞背景特异性信号传导。总体情况表明食欲素受体信号传导具有高度的内在多样性。
在本章中,我将介绍细胞和分子水平上的食欲素信号传导。由于这些内容是本书其他章节的重点,因此关于与(潜在的)生理性食欲素反应的联系的讨论将非常简短。突触后信号传导机制也是如此,这在布尔达科夫的《食欲素的突触后作用》中有论述。本章根据组织类型进行编排,从中枢神经系统开始。最后,将讨论跨组织、细胞类型甚至物种的受体信号传导途径。