Chloroethylclonidine reveals that α1A-adrenoceptors mediate contraction in aorta of α1D-adrenoceptor knockout mice

1 We have characterized the α 1 -adrenoceptor subtypes present in isolated aorta of the α 1 D -adrenoceptor knockout (KO) mice, by chloroethylclonidine (CEC)-induced alkylation and their protection by selective α 1 -adrenoceptor antagonists. 2 The α 1 D -adrenoceptor is involved in the contractile response to noradrenaline in wild type (WT) mouse aorta. 3 In WT mice 5-methylurapidil (5-MU, an α 1 A -adrenoceptor antagonist) or BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-8-azaspiro[4.5] decane-7,9 dione, a selective α 1 D -adrenoceptor antagonist), protected the receptors from CEC-induced (α 1 B / D -adrenoceptor) alkylation, the combination of both antagonists resulted in complete protection, while AH11110A (1-[biphenyl-2-yloxy]-4-imino-4-piperidin-1-yl-butan-2-ol, an α 1 B -adrenoceptor antagonist) did not protect. 4 In aorta of KO mice there was a 19-fold rightward shift in noradrenaline effective concentration (EC 5 0 ) compared with WT; while 5-MU alone or in combination with AH11110A protected α 1 -adrenoceptors to the same extent. 5 The data indicate that α 1 A -adrenoceptors mediate contraction and suggest their role in maintaining homeostasis in the α 1 D -adrenoceptors KO mice.