“…However, even in the early studies it was evident that there was regional and species variation in the affinity of a-adrenoceptor subtype-selective drugs competing for binding of the a,-adrenoceptor antagonist ligand [3H]rauwolscine (Cheung et al, 1982;Summers et al, 1983;Kawahara and Bylund, 1985;Neylon and Summers, 1985). Subsequent studies with solubilized receptors, eliminating possible contributions from other components of membranes, confirmed these findings (Cheung et al, 1986). The presence of multiple a,-adrenoceptor subtypes is supported by several lines of evidence, the strongest of which are the cloning and sequencing of four a,-adrenoceptors, the development of subtypespecific drugs such as SKF 104078 (Ruff010 et al, 1987), and the characterization of several cell lines that express a single subtype .…”