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Modulation of [ 3 H]Acetylcholine Release from Cultured Amacrine‐Like Neurons by Adenosine A 1 Receptors
Author(s) -
Santos Paulo F.,
Santos Maria S.,
Carvalho Arsélio P.,
Duarte Carlos B.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71031086.x
Subject(s) - adenosine , adenosine deaminase , adenosine receptor , adenosine a1 receptor , purinergic signalling , acetylcholine , extracellular , chemistry , adenosine a2b receptor , depolarization , medicine , adenosine a3 receptor , muscarinic acetylcholine receptor , receptor , endocrinology , biophysics , biochemistry , biology , agonist
We have investigated the effect of endogenous adenosine on the release of [ 3 H]acetylcholine ([ 3 H]ACh) in cultured chick amacrine‐like neurons. The release of [ 3 H]ACh evoked by 50 m M KCl was mostly Ca 2+ dependent, and it was increased in the presence of adenosine deaminase and in the presence of 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX), an adenosine A 1 receptor antagonist. The effect of adenosine on [ 3 H]ACh release was sensitive to pertussis toxin (PTX) and was due to a selective inhibition of N‐type Ca 2+ channels. Ligand binding studies using [ 3 H]DPCPX confirmed the presence of adenosine A 1 receptors in the preparation. Using specific inhibitors of the plasma membrane adenosine carriers and of the ectonucleotidases, we found that the extracellular accumulation of adenosine in response to KCl depolarization was due to the release of endogenous adenosine per se and to the extracellular conversion of released nucleotides into adenosine. Activation of adenosine A 1 receptors was without effect on the intracellular levels of cyclic AMP under depolarizing conditions, but it inhibited the accumulation of inositol phosphates. Our results indicate that in cultured amacrine‐like neurons, the Ca 2+ ‐dependent release of [ 3 H]ACh evoked by KCl is under tonic inhibition by adenosine, which activates A 1 receptors. The effect of adenosine on the [ 3 H]ACh release may be due to a direct inhibition of N‐type Ca 2+ channels and/or secondary to the inhibition of phospholipase C and involves the activation of PTX‐sensitive G proteins.