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Studies on the stereoselectivity of the P 2 ‐purinoceptor
Author(s) -
Burnstock G.,
Cusack N.J.,
Hills J.M.,
MacKenzie I.,
Meghji P.
Publication year - 1983
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.1476-5381.1983.tb10535.x
Subject(s) - taenia coli , stereoselectivity , guinea pig , purinergic receptor , stereospecificity , enantiomer , chemistry , adenosine , ventricle , stereochemistry , medicine , endocrinology , biology , biochemistry , catalysis
1 ATP, 2‐chloro‐ATP, 2‐methylthio‐ATP, and their unnatural L ‐enantiomers, were synthesized and their effects tested on the guinea‐pig taenia coli and urinary bladder, and the stimulated frog ventricle. 2 The potent P 2 ‐purinoceptor agonists, 2‐chloro‐ATP and 2‐methylthio‐ATP were, respectively, 30 and 200 times more effective than ATP in relaxing the guinea‐pig taenia, but approximately as effective as ATP in contracting the guinea‐pig bladder and augmenting the force of contraction of the frog ventricle. 3 A high degree of stereoselectivity was observed for relaxations of the guinea‐pig taenia coli produced by the P 2 ‐purinoceptoragonists, and 2‐methylthio‐ATP was over 700 times more effective than its L ‐enantiomer. In contrast, stereoselectivity for contraction of the guinea‐pig bladder was observed only at low concentrations with each pair of enantiomers, and a similar low stereoselectivity was displayed by the frog ventricle. 4 These results show that P 2 ‐purinoceptors mediating inhibitory responses in the guinea‐pig taenia coli can show a high degree of stereoselectivity, while P 2 ‐purinoceptors mediating excitatory responses in the guinea‐pig bladder and in the frog ventricle show little stereoselectivity. 5 The partial stereoselectivity of the P 2 ‐purinoceptor in smooth muscle contrasts with the absolute stereospecificity of P 1 ‐purinoceptors for adenosine on smooth muscle and autonomic nerve terminals and the absolute stereospecificity of the receptor for ADP on the human platelet.