Different subtypes of α_(1A)-adrenoceptor mediating contraction of rat epididymal vas deferens, rat hepatic portal vein and human prostate distinguished by the antagonist RS 17053

摘要

1 The α_1-adrenoceptor subtype mediating contraction of the rat hepatic portal vein to phenylephrine was characterized by use of competitive antagonists previously shown to have selectivity between the expressed α_1-subtype clones. Prazosin competitively antagonized the phenylephrine contractions with a pA_2 value of 9.2, as did WB 4101 (pA_2 9.4), 5-methyl urapidil (pA_2 8.6), indoramin (pA_2 8.4) and BMY 7378 (pA_2 6.5). 2 The pA_2 values on the rat portal vein correlated highly with their previously published pA_2 values for the α_(1A)-adrenoceptors mediating contraction of the rat epididymal vas deferens and human prostate and poorly with those for the α_(1B)- and α_(1D)-adrenoceptors mediating contraction of the rat spleen and aorta, respectively. The antagonist pA_2 values on the rat portal vein correlated highly with their previously published pK_1 values for the expressed α_(1a)-clone and poorly with those for the expressed α_(1b)- and α_(1d)-clones. Therefore the results show that contraction of the rat portal vein to phenylephrine is mediated by α_(1A)-adrenoceptors. 3 The novel α_1-adrenoceptor antagonist RS 17053 had a relatively high affinity for the α_(1A)-adrenoceptors mediating contraction of the rat epididymal vas deferens (pA_2 9.5) compared with the α_(1B)-adrenoceptors in the rat spleen (pA_2 7.2) or the α_(1D)-adrenoceptors in the rat aorta (pK_B 7.1), in agreement with its selectivity for the expressed α_(1a)-clone. However, RS 17053 had over 100 fold lower affinity for the α_(1A)-adrenoceptors mediating contraction of the rat portal vein (pK_B 7.1) and human prostate (pK_B 7.1) compared with its affinity for the α_(1A)-adrenoceptors in the rat epididymal vas deferens or the expressed α_(1a)-clone. 4 The difference in affinity of RS 17053 between the rat epididymal vas deferens and rat portal vein cannot be explained by a species difference in the receptor. Therefore RS 17053 may distinguish between subtypes of the α_(1A)-adrenoceptor in the rat portal vein and human prostate compared with those in the rat epididymal vas deferens or the expressed α_(1a)-clone.