Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
Br J Pharmacol. 2019 Jul;176(14):2358-2365. doi: 10.1111/bph.14599. Epub 2019 Mar 27.
The α -adrenoceptor is abundantly expressed in the lower urinary tract and is the principal therapeutic target for the symptomatic treatment of lower urinary tract symptoms in men. Prazosin has a lower affinity for the lower urinary tract α -adrenoceptor than α -adrenoceptors found in other parts of the body. This has led to the lower urinary tract α -adrenoceptor being subclassified as an α -adrenoceptor. It was demonstrated that this pharmacologically distinct α -adrenoceptor is a product of the α -adrenoceptor gene, but the mechanism by which this altered phenotype is achieved remains a mystery. Hypotheses for this altered pharmacology include the presence of an interacting protein such as cysteine-rich with EGF-like domain (CRELD) 1 or other GPCRs such as the CXCR2 chemokine or 5-HT receptor. Alternatively, the influence of breast cancer resistance protein (BCRP) efflux transporters on the pharmacology of α -adrenoceptors has also been investigated. These and other hypotheses will be described and discussed in this review. LINKED ARTICLES: This article is part of a themed section on Adrenoceptors-New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc.
α-肾上腺素受体在泌尿系统中大量表达，是男性下尿路症状对症治疗的主要靶点。哌唑嗪对下尿路 α-肾上腺素受体的亲和力低于身体其他部位的 α-肾上腺素受体。这导致将下尿路 α-肾上腺素受体分为 α-肾上腺素受体亚类。已经证明，这种药理学上不同的 α-肾上腺素受体是 α-肾上腺素受体基因的产物，但实现这种改变表型的机制仍然是一个谜。对于这种改变的药理学的假设包括存在相互作用的蛋白质，如富含半胱氨酸的表皮生长因子样域 1（CRELD1）或其他 GPCR，如 CXCR2 趋化因子或 5-HT 受体。或者，乳腺癌耐药蛋白（BCRP）外排转运体对 α-肾上腺素受体的药理学的影响也进行了研究。这些和其他假设将在本综述中进行描述和讨论。 相关文章：本文是关于肾上腺素能受体-旧角色的新角色的专题部分的一部分。要查看本节中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc.
