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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
Author(s) -
Marshall Ian,
Burt Richard P.,
Green G. Mark,
Hussain Monira B.,
Chapple Christopher R.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb16001.x
Subject(s) - vas deferens , phenylephrine , prazosin , contraction (grammar) , endocrinology , medicine , antagonist , biology , hepatic portal vein , portal vein , receptor , blood pressure
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 p K 1 values for the expressed α 1a ‐clone and poorly with those for the expressed α 1b ‐ and α1 d ‐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 (p K 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 (p K B 7.1) and human prostate (p K 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.