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Effect of Adenosine, Adenosine Derivatives, and Caffeine on Acetylcholine Release from Brain Synaptosomes: Interaction with Muscarinic Autoregulatory Mechanisms
Author(s) -
Pedata Felicita,
Giovannelli Lisa,
Sarno Patrizia,
Pepeu Giancarlo
Publication year - 1986
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 - 10.1111/j.1471-4159.1986.tb01781.x
Subject(s) - adenosine , oxotremorine , acetylcholine , chemistry , muscarinic acetylcholine receptor , medicine , endocrinology , caffeine , adenosine receptor , inhibitory postsynaptic potential , synaptosome , biochemistry , biology , receptor , agonist , in vitro
Synaptosomes, prepared from rat cerebral cortex and hippocampus, were preincubated with [ methyl ‐ 3 H]choline. The effect of adenosine, cyclohexyl‐adenosine, N ‐ethylcarboxamide adenosine, 2′‐deoxyadenosine, and oxotremorine on K + ‐evoked 3 H efflux was investigated. High‐voltage electrophoretic separation showed that in the presence of physostigmine, the K + ‐evoked 3 H efflux from hippocampal synaptosomes was 90% [ 3 H]acetylcholine and 10% [ 3 H]choline. Adenosine (30 μ M ) and oxotremorine (100 μ M ) both decreased [ 3 H]acetylcholine release from hippocampal synaptosomes. The effect was inversely proportional to the KCI concentration and disappeared at a KCI concentration of 50 m M. Cyclohexyladenosine was ∼3,000 times more active then adenosine, whereas N ‐ethylcarboxamide adenosine and 2′‐deoxyadenosine were inactive. This indicates that A 1 adenosine receptors were involved in the inhibitory effect. Caffeine antagonized the adenosine effect, and at a concentration of 100 μ M , it stimulated [ 3 H]acetylcholine efflux. The inhibitory effect of oxotremorine was as great in cortical as in hippocampal synaptosomes. In contrast, adenosine was much less active in cortical than in hippocampal synaptosomes. When inhibitory concentrations of adenosine and oxotremorine were added together into the incubation medium, the effect of adenosine on [ 3 H]acetylcholine release was consistently reduced. An interaction between muscarinic and A 1 adenosine presynaptic receptors at a common site modulating acetylcholine release can be assumed.