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What makes the α 1A ‐adrenoceptor gene product assume an α 1L ‐adrenoceptor phenotype?
Author(s) -
White Carl W.,
Junior Edilson Dantas,
Lim Linzi,
Ventura Sabatino
Publication year - 2019
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.14599
Subject(s) - phenotype , prazosin , urinary system , adrenergic receptor , biology , receptor , g protein coupled receptor , endocrinology , medicine , gene , bioinformatics , pharmacology , genetics , antagonist
The α 1A -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 1A -adrenoceptor than α 1A -adrenoceptors found in other parts of the body. This has led to the lower urinary tract α 1A -adrenoceptor being subclassified as an α 1L -adrenoceptor. It was demonstrated that this pharmacologically distinct α 1L -adrenoceptor is a product of the α 1A -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 1B receptor. Alternatively, the influence of breast cancer resistance protein (BCRP) efflux transporters on the pharmacology of α 1A -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.