Premium
Inhibition by KF17837 of adenosine A 2A receptor‐mediated modulation of striatal GABA and ACh release
Author(s) -
Kurokawa Masako,
Kirk Ian P.,
Kirkpatrick Karen A.,
Kase Hiroshi,
Richardson Peter J.
Publication year - 1994
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.1476-5381.1994.tb16171.x
Subject(s) - cgs 21680 , bicuculline , chemistry , endocrinology , medicine , adenosine , agonist , (+) naloxone , adenosine receptor , gaba receptor antagonist , adenosine a1 receptor , pharmacology , antagonist , receptor , biology , biochemistry
1 The effect of the A 2A adenosine receptor agonist, 2‐ p ‐(‐2‐carboxyethyl)phenethyl‐amino‐5′‐N‐ethylcarboxamidoadenosine (CGS 21680) on the potassium evoked release of [ 3 H]‐γ‐aminobutyric acid ([ 3 H]‐GABA) from nerve terminals derived from the caudate‐putamen and the globus pallidus of the rat was compared. In both preparations CGS 21680 (1 n m ) inhibited the [ 3 H]‐GABA release evoked by 15 m m KCl but had no effect on that evoked by 30 m m KCl. 2 The ability of CGS 21680 (1 n m ) to inhibit the release of [ 3 H]‐GABA from striatal nerve terminals was unaffected by the presence of the GABA receptor antagonists, bicuculline (10 μ m ), phaclofen (100 μ m ) and 2‐hydroxysaclofen (100 μ m ). Similarly the opioid receptor antagonist, naloxone (10 μ m ), the adenosine A 1 receptor antagonist, 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX, 40 n m ), and the cholinoceptor antagonists, mecamylamine (10 μ m ) and atropine (100 n m ) had no effect on this inhibition. 3 The ability of CGS 21680 (0.1 n m ) to stimulate the release of [ 3 H]‐acetylcholine ([ 3 H]‐ACh) from striatal nerve terminals was unaffected by the presence of bicuculline (10 μ m ), 2‐hydroxysaclofen (100 μ m ), phaclofen (100 μ m ), naloxone (10 μ m ) and DPCPX (4 nM). 4 The novel A 2A receptor antagonist, (E)‐8‐(3,4‐dimethoxystyryl)‐1,3‐dipropyl‐7‐methylxanthine (KF 17837), blocked the CGS 21680 (1 n m )‐induced inhibition of [ 3 H]‐GABA efflux with an EC 50 of approximately 30 n m and also antagonized the CGS 21680 (0.1 n m )‐induced stimulation of [ 3 H]‐ACh release with an EC 50 of approximately 0.3 n m . 5 It is concluded that the A 2A adenosine receptor is present on both GABAergic and cholinergic nerve terminals of the rat striatum and that in both the caudate‐putamen and the globus pallidus this receptor inhibits [ 3 H]‐GABA release. No evidence was seen for a difference in the ligand binding sites of this receptor in the two groups of nerve terminals.