The α1L-adrenoceptor is an alternative phenotype of the α1A-adrenoceptor gene

Despite over two decades of research, the molecular identity of the α1L-adrenoceptor phenotype has remained elusive. Gray et al. (2008) present results in this issue of the journal that provide persuasive evidence that the in vivo α1L-adrenoceptor phenotype requires the expression of the α1A-adrenoceptor gene. They have shown that in mice lacking the functional α1A-adrenoceptor gene, α1L-mediated responses to noradrenaline in prostate smooth muscle are substantially attenuated. These findings support earlier evidence that the α1L-adrenoceptor profile represents a functional phenotype of the α1A-adrenoceptor gene product, but additional cell backgrounddependent factors must act in concert with the α1A-adrenoceptor protein to determine whether an α1Lor a classical α1A-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.