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Functional coupling between A 1 adenosine receptors and G‐proteins in rat hippocampal membranes assessed by high‐affinity GTPase activity
Author(s) -
Odagaki Y.,
Fuxe K.
Publication year - 1995
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.1476-5381.1995.tb17228.x
Subject(s) - adenosine , adenosine receptor , adenosine a1 receptor , adenosine a2b receptor , receptor , g protein coupled receptor , agonist , cgs 21680 , biology , adenosine a3 receptor , gtpase , purinergic signalling , chemistry , biochemistry
1 In order to investigate the functional interaction between adenosine receptors and G‐proteins in native brain membranes, stimulation of high‐affinity GTPase activity by adenosine receptor agonists was characterized in rat hippocampal membranes. 2 Addition of 1 μ m R‐N 6 phenylisopropyladenosine (R‐PIA), a selective A 1 adenosine receptor agonist, augmented the V max of the low‐ K M GTPase by 51, with a slight increase in the K M value. 3 Several adenosine receptor agonists stimulated the high‐affinity GTPase activity in a concentration‐dependent manner, with a rank order of potency indicative of the involvement of A 1 adenosine receptor subtype as follows: R‐PIA > N 6 ‐cyclohexyladenosine > 5′‐N‐ethylcarboxamidoadenosine ≤ 2‐chloroadeno‐sine>S‐PIA>CGS 21680, 2‐phenylaminoadenosine. 4 The selective A 1 adenosine receptor antagonist, 8‐cyclopentyl‐1,3‐dipropylxanthine, inhibited R‐PIA‐stimulated high‐affinity GTPase activity in a competitive manner, with a K B value of 2.5 n m . 5 The activating effects on high‐affinity GTPase of R‐PIA (via A 1 adenosine receptors) and of 5‐HT (via 5‐HT 1A receptors) were completely additive, indicating that A 1 adenosine and 5‐HT 1A receptors were coupled to distinct pools of G‐proteins in hippocampus. 6 Stimulation of high‐affinity GTPase activity by adenosine receptor agonists can be used as a valuable measure for the investigation of the functional coupling between A 1 adenosine receptors and G‐proteins associated with adenylyl cyclase inhibition.