TY - JOUR T1 - OPC-28326, a Selective Femoral Vasodilator, Is an α<sub>2C</sub>-Adrenoceptor-Selective Antagonist JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 652 LP - 658 VL - 299 IS - 2 AU - Bing Sun AU - Simon Lockyer AU - Jess Li AU - Ruoyan Chen AU - Masuhiro Yoshitake AU - Jun-Ichi Kambayashi Y1 - 2001/11/01 UR - http://jpet.aspetjournals.org/content/299/2/652.abstract N2 - OPC-28326 has been reported to selectively increase femoral blood flow in open-chest dogs and autoperfused canine femoral artery preparations. Preliminary data indicated that OPC-28326 has a high affinity at the α2-adrenoceptor. In the present study, we tested OPC-28326 in isoflurane anesthetized rats at a dose of 3 mg/kg of body weight, given intraduodenally. OPC-28326 significantly increased femoral blood flow, by 44.7 ± 13.8%, 45 min after drug administration, whereas carotid blood flow increased by only 3.6 ± 5.5% (n = 6). Chinese hamster ovary cell lines overexpressing rat α2D-, α2B-, or α2C-adrenoceptor were established. These cells also coexpress luciferase, driven by cAMP elevation. In radioligand binding assays using cell membrane preparations, OPC-28326 dose dependently competed with [3H]RX821002 binding, with calculatedKi values of 3840 ± 887, 633 ± 46, and 13.7 ± 1.9 nM on α2D-, α2B-, and α2C-adrenoceptor, respectively. A similar affinity and rank order of potency were also found for OPC-28326 on the α2-subtypes using epinephrine as agonist in luciferase assays. No agonistic effect of OPC-28326 was detected on any of the α2-adrenoceptors. Finally, in situ hybridization performed on skeletal muscle tissue sections collected from rat hind limb (musculus gastrocnemius) demonstrated a high level expression of α2C in the vascular tissues. Thus, the abundance of α2C in the skeletal muscle may account for the selective effect of OPC-28326 in increasing femoral blood flow. The American Society for Pharmacology and Experimental Therapeutics ER -