What makes the α1A-adrenoceptor gene express the α1L-adrenoceptor functional phenotype?

The a1A-adrenoceptor is therapeutically exploited because of its prevalence in the lower urinary tract. The pharmacology shown by this lower urinary tract a1A-adrenoceptor is different from that shown by other a1A-adrenoceptors, which has led to it being subclassified as an a1L-adrenoceptor. Only in the last few years was it shown that this pharmacologically distinct a1L-adrenoceptor is a product of the a1A-adrenoceptor gene. In this issue of the BJP, Nishimune et al. review the literature on a1L-adrenoceptor pharmacology and discuss the possible molecular mechanisms by which the a1A-adrenoceptor gene is able to produce two pharmacologically distinct adrenoceptor subtypes. Based primarily from their own research using cell lines transfected with a1A-adrenoceptors, they conclude that a protein that interacts with the receptor is the most plausible explanation. The challenge remains to identify any such interacting protein and show how it is able to change the pharmacology of the receptor for different ligands.