The α 1L ‐adrenoceptor is an alternative phenotype of the α 1A ‐adrenoceptor

Despite over two decades of research, the molecular identity of the α 1L ‐adrenoceptor phenotype has remained elusive. In this issue of the BJP , Gray et al. (2008) provide persuasive evidence that the in vivo α 1L ‐adrenoceptor phenotype requires the expression of the α 1A ‐adrenoceptor gene. They have shown that in mice lacking the functional α 1A ‐adrenoceptor gene, α 1L ‐mediated responses to noradrenaline in prostate smooth muscle are substantially attenuated. These findings support earlier evidence that the α 1L ‐adrenoceptor profile represents a functional phenotype of the α 1A ‐adrenoceptor gene product, but additional cell background‐dependent factors must act in concert with the α 1A ‐adrenoceptor protein to determine whether an α 1L ‐ or a classical α 1A ‐adrenoceptor profile is expressed. The challenge remains to establish the nature of these cellular factors and the mechanism(s) by which they influence G‐protein‐coupled receptor pharmacology. British Journal of Pharmacology (2008) 155 , 1–3; doi: fn1 ; published online 23 June 2008