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Studies on the adenosine‐receptor mediating the augmentation of histamine‐induced inositol phospholipid hydrolysis in guinea‐pig cerebral cortex
Author(s) -
Hill S.J.,
Kendall D.A.
Publication year - 1987
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.1476-5381.1987.tb11260.x
Subject(s) - adenosine , histamine , xanthine , agonist , inositol phosphate , medicine , endocrinology , carbachol , adenosine a1 receptor , adenosine receptor , chemistry , inositol , stimulation , receptor , biology , biochemistry , enzyme
1 Incubation (45 min) of slices of guinea‐pig cerebral cortex with adenosine alone had no significant effect on the accumulation of [ 3 H]‐inositol phosphates but enhanced the response to histamine H 1 ‐receptor stimulation in a concentration‐dependent manner. 2 The effect of adenosine on agonist‐stimulated inositol phospholipid hydrolysis appeared to be selective for histamine H 1 ‐receptor stimulation since it did not augment the phosphoinositide responses to carbachol, noradrenaline, 5‐hydroxytryptamine or elevated KC1. 3 The accumulation of [ 3 H]‐inositol phosphates induced by histamine increased linearly between 5 and 45 min incubation with agonist. However, following the simultaneous addition of histamine and adenosine, there was a marked delay in the appearance of the augmentation produced by adenosine. 4 The augmentation of [ 3 H]‐inositol phosphate accumulation was mimicked by a number of adenosine analogues. The rank order of potency was; cyclopentyladenosine > R ‐phenylisopropyladenosine > 5′‐N‐ethylcarboxamidoadenosine > 2‐chloroadenosine. This is consistent with the order expected for an adenosine A 1 ‐receptor effect but the EC 50 values were in the micro‐rather than nanomolar range. 5 The response to 2‐chloroadenosine was antagonized by the xanthine adenosine‐antagonists, cyclopropyltheophylline, 8‐phenyltheophylline, 3‐isobutyl‐1‐methylxanthine and theophylline, and the non‐xanthine alloxazine.