TY - JOUR T1 - Identification of α-1L Adrenoceptor in Rabbit Ear Artery JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 995 LP - 1002 DO - 10.1124/jpet.104.066985 VL - 310 IS - 3 AU - Yasuko Hiraizumi-Hiraoka AU - Takashi Tanaka AU - Hatsumi Yamamoto AU - Fumiko Suzuki AU - Ikunobu Muramatsu Y1 - 2004/09/01 UR - http://jpet.aspetjournals.org/content/310/3/995.abstract N2 - The α-1L adrenoceptor (AR) was identified in rabbit ear artery by both functional and ligand binding studies. In functional studies using arterial rings, the contractile response to NS-49 [(R)-(-)-3′-(2-amino-1-hydroxyethyl)-4′-fluorometh-anesulfonanilide hydrochloride] (α-1A and α-1L AR-selective agonist) was competitively antagonized with low affinities by prazosin, RS-17053 [N-[2-(2-cyclopropylmethoxyphenoxy) ethyl]-5-chloro-α,α-dimethyl-1H-indole-3-ethamine hydrochloride], and 5-methylurapidil but with high affinities by tamsulosin and KMD-3213 [(-)-1-(3-hydroxypropyl)-5-[(2R)-2-({2-[(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7-carboxamide]. In contrast, the response to noradrenaline (nonselective α-1 AR agonist) was inhibited noncompetitively by these antagonists (except 5-methylurapidil) with Schild slopes different from unity. These results suggest that the response to NS-49 was mediated predominantly via α-1L ARs, whereas the response to noradrenaline was produced through two distinct α-1 AR subtypes (presumably α-1B and α-1L ARs). In binding studies with intact segments of rabbit ear artery, [3H]KMD-3213 bound with high affinity (pKD = 9.7) to α-1 ARs, which were subdivided by prazosin, RS-17053, and 5-methylurapidil into two subtypes (α-1A and α-1L ARs). In contrast, [3H]prazosin binding sites in ear artery segments (pKD = 9.8) were identified as α-1A and α-1B ARs. In conventional binding studies using isolated rabbit ear artery microsomal membranes, [3H]KMD-3213 binding sites were identified as α-1A ARs with high affinities for prazosin, RS-17053, and 5-methylurapidil. Our study indicates that an α-1L AR having a unique pharmacological profile coexists with α-1A and α-1B ARs in rabbit ear artery and can be identified either functionally or by binding studies using intact tissues but not microsomal membrane preparations. The American Society for Pharmacology and Experimental Therapeutics ER -