Passani Maria Beatrice, Lin Jian-Sheng, Hancock Arthur, Crochet Sylvain, Blandina Patrizio
Dipartimento di Farmacologia Preclinica e Clinica, Universitá di Firenze, Viale Pieraccini 6, 50139 Firenze, Italy.
Trends Pharmacol Sci. 2004 Dec;25(12):618-25. doi: 10.1016/j.tips.2004.10.003.
Histamine H3 receptor pharmacology, functions and biochemistry are far from being fully understood; however, progress is being made. Activation of this Gi/GO-protein-coupled receptor affects cognition, the sleep-wake cycle, obesity and epilepsy, which are physiological and pathological conditions that are the main focus of research into the therapeutic potential of selective H3 receptor ligands. This heterogeneity of targets can be reconciled partially by the fact that the histamine system constitutes one of the most important brain-activating systems and that H3 receptors regulate the activity of histamine and other neurotransmitter systems. Furthermore, the H3 receptor shows functional constitutive activity, polymorphisms in humans and rodents with a differential distribution of splice variants in the CNS, and potential coupling to different intracellular signal transduction mechanisms. In light of the genetic, pharmacological and functional complexity of the H3 receptor, the importance of the histamine system as a therapeutic target to control the sleep-wake cycle and cognitive disorders will be discussed.
组胺H3受体的药理学、功能及生物化学远未被完全理解；然而，目前正在取得进展。这种与Gi/GO蛋白偶联的受体的激活会影响认知、睡眠-觉醒周期、肥胖症和癫痫，这些生理和病理状况是选择性H3受体配体治疗潜力研究的主要焦点。组胺系统是最重要的脑激活系统之一，且H3受体调节组胺及其他神经递质系统的活性，这一事实可部分解释这种靶点的异质性。此外，H3受体表现出功能性组成活性、人类和啮齿动物中的多态性以及中枢神经系统中剪接变体的差异分布，并且可能与不同的细胞内信号转导机制偶联。鉴于H3受体的遗传、药理学和功能复杂性，将讨论组胺系统作为控制睡眠-觉醒周期和认知障碍的治疗靶点的重要性。
