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.
Nelson
Cp
C
Department of Cell Physiology and Pharmacology, University of Leicester, Henry Wellcome Building, Leicester, UK. cpn5@le.ac.uk
D000818:Animals; D005838:Genotype; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D010641:Phenotype; D011467:Prostate / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
C547714:Adra1a protein, mouse; D018340:Receptors, Adrenergic, alpha-1; D009638:Norepinephrine