What makes the α 1A -adrenoceptor gene product assume an α 1L -adrenoceptor phenotype?

• Published in: British journal of pharmacology Vol. 176; no. 14; pp. 2358 - 2365
• Main Authors: White, Carl W, da Silva Junior, Edilson Dantas, Lim, Linzi, Ventura, Sabatino
• Format: Journal Article
• Language: English
• Published: England 01.07.2019
• Subjects: Animals; Humans; Phenotype; Receptors, Adrenergic, alpha-1 - genetics
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/bph.14599

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.