The alpha1L-adrenoceptor is an alternative phenotype of the alpha1A-adrenoceptor

Despite over two decades of research, the molecular identity of the alpha1L-adrenoceptor phenotype has remained elusive. In this issue of the BJP, Gray et al. (2008) provide persuasive evidence that the in vivo alpha1L-adrenoceptor phenotype requires the expression of the alpha1A-adrenoceptor gene. They have shown that in mice lacking the functional alpha1A-adrenoceptor gene, alpha1L-mediated responses to noradrenaline in prostate smooth muscle are substantially attenuated. These findings support earlier evidence that the alpha(1L)-adrenoceptor profile represents a functional phenotype of the alpha(1A)-adrenoceptor gene product, but additional cell background-dependent factors must act in concert with the alpha(1A)-adrenoceptor protein to determine whether an alpha(1L)- or a classical alpha(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.