Different subtypes of α1A‐adrenoceptor mediating contraction of rat epididymal vas deferens, rat hepatic portal vein and human prostate distinguished by the antagonist RS 17053

• Published in: British journal of pharmacology 1996-09, Vol.119 (2), p.407-415
• Main Authors: Marshall, Ian, Burt, Richard P., Green, G. Mark, Hussain, Monira B., Chapple, Christopher R.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cell receptors; Cell structures and functions; Fundamental and applied biological sciences. Psychology; human prostate; Molecular and cellular biology; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine); rat epididymal vas deferens; rat hepatic portal vein; RS 17053; α1A‐adrenoceptors; α1‐adrenoceptor subtypes
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1996.tb16001.x

1 The α1‐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 α1‐subtype clones. Prazosin competitively antagonized the phenylephrine contractions with a pA2 value of 9.2, as did WB 4101 (pA2 9.4), 5‐methyl urapidil (pA2 8.6), indoramin (pA2 8.4) and BMY 7378 (pA2 6.5). 2 The pA2 values on the rat portal vein correlated highly with their previously published pA2 values for the α1A‐adrenoceptors mediating contraction of the rat epididymal vas deferens and human prostate and poorly with those for the α1B‐ and α1D‐adrenoceptors mediating contraction of the rat spleen and aorta, respectively. The antagonist pA2 values on the rat portal vein correlated highly with their previously published pK1 values for the expressed α1a‐clone and poorly with those for the expressed α1b‐ and α1d‐clones. Therefore the results show that contraction of the rat portal vein to phenylephrine is mediated by α1A‐adrenoceptors. 3 The novel α1‐adrenoceptor antagonist RS 17053 had a relatively high affinity for the α1A‐adrenoceptors mediating contraction of the rat epididymal vas deferens (pA2 9.5) compared with the α1B‐adrenoceptors in the rat spleen (pA2 7.2) or the α1D‐adrenoceptors in the rat aorta (pKB 7.1), in agreement with its selectivity for the expressed α1a‐clone. However, RS 17053 had over 100 fold lower affinity for the α1A‐adrenoceptors mediating contraction of the rat portal vein (pKB 7.1) and human prostate (pKB 7.1) compared with its affinity for the α1A‐adrenoceptors in the rat epididymal vas deferens or the expressed α1a‐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 α1a‐adrenoceptor in the rat portal vein and human prostate compared with those in the rat epididymal vas deferens or the expressed α1a‐clone.