What makes the α1A‐adrenoceptor gene product assume an α1L‐adrenoceptor phenotype?

The α1A‐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 α1A‐adrenoceptor than α1A‐adrenoceptors found in other parts of the body. This has led to the lower urinary tract α1A‐adrenoceptor being subclassified as an α1L‐adrenoceptor. It was demonstrated that this pharmacologically distinct α1L‐adrenoceptor is a product of the α1A‐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‐HT1B receptor. Alternatively, the influence of breast cancer resistance protein (BCRP) efflux transporters on the pharmacology of α1A‐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