Hancock Arthur A, Esbenshade Timothy A, Krueger Kathleen M, Yao Betty Bei
Neuroscience Research, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6125, USA.
Life Sci. 2003 Oct 31;73(24):3043-72. doi: 10.1016/j.lfs.2003.06.003.
Histaminergic H3 receptors modulate the release of neurotransmitters within the CNS and periphery. Ligands for these receptors have potential clinical utility in a variety of disease states. However, the pharmacological characteristics of these receptors have been enigmatic for more than a decade because of the diversity of pharmacological effects observed with the limited number of heretofore-available compounds. Recent cloning of the H3 receptor has revealed interspecies differences in the protein sequences in key regions, the existence of splice variants that differ in composition between species, and potential differences in signal transduction processes between either different tissues and/or species. This review attempts to summarize these findings within the context of the molecular biological and pharmacological data accumulated to date. Also, we suggest a nomenclature strategy to reduce potential confusion that has arisen from different naming systems used by various investigators. While some facets of this genetic and pharmacological diversity help to rationalize various aspects of H3 receptor heterogeneity, there remains an insufficient repertoire of selective ligands, assays, or other measures to completely resolve all components of this diversity. The promise of newly available tools to further explore H3 receptor function may provide the insight to bring the promised clinical potential of H3 receptor ligands to realization.
组胺能H3受体调节中枢神经系统和外周神经递质的释放。这些受体的配体在多种疾病状态下具有潜在的临床应用价值。然而，由于迄今可用的化合物数量有限，观察到的药理作用具有多样性，这些受体的药理学特性在十多年来一直是个谜。最近克隆的H3受体揭示了关键区域蛋白质序列的种间差异、不同物种间组成不同的剪接变体的存在，以及不同组织和/或物种间信号转导过程的潜在差异。本综述试图在迄今为止积累的分子生物学和药理学数据的背景下总结这些发现。此外，我们提出一种命名策略，以减少不同研究者使用不同命名系统所产生的潜在混淆。虽然这种遗传和药理学多样性的某些方面有助于解释H3受体异质性的各个方面，但选择性配体、检测方法或其他措施的种类仍然不足，无法完全解决这种多样性的所有组成部分。新可用工具进一步探索H3受体功能的前景可能会提供深入了解，使H3受体配体的预期临床潜力得以实现。
