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Effect of Presynaptic P 2 Receptor Stimulation on Transmitter Release
Author(s) -
Sperlagh B.,
Vizi E. S.
Publication year - 1991
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.1471-4159.1991.tb02039.x
Subject(s) - acetylcholine , adenosine , agonist , stimulation , purinergic receptor , chemistry , receptor , adenosine receptor , medicine , endocrinology , muscarinic acetylcholine receptor , cholinergic , biology , biochemistry
Because ATP is degraded to adenosine, its effect could be mediated by both P] and P 2 receptors. Hence, the actions of an ATP analogue, resistant to enzymatic breakdown (α,β‐methylene ATP), were studied on the resting and electrically evoked release of radioactivity from longitudinal muscle strips of guinea pig ileum, preloaded either with [ 3 H]choline or with [ 3 H]noradrenaline. Their effects were compared with the actions of adenosine and ATP. Although adenosine and ATP markedly decreased the [ 3 H]acetylcholine release evoked by field stimulation, α,β‐methylene‐ATP, a potent and selective agonist of P 2x receptors, enhanced’ this release. However, 2‐methyl‐2‐thio‐ATP, an agonist of the P 2y receptors, neither enhanced nor inhibited the [ 3 H]‐acetylcholine release. 8‐Phenyltheophylline, an antagonist of P I receptors, increased the stimulation‐evoked release of acetylcholine, indicating that the release of acetylcholine is ton‐ically controlled by endogenous adenosine via PI receptors. When α,β‐methylene‐ATP and 8‐phenyltheophylline were added together, their potentiating effect on the acetylcholine release proved to be additive. Because α,β‐methylene‐ATP failed to antagonize the presynaptic effect of adenosine on PI purinoceptors, it seems very likely that its effect to enhance transmitter release is mediated via separate receptors, i.e., via P 2x receptors, located on the axon terminals. Similarly, the stimulation‐evoked release of [ 3 H]noradrenaline was enhanced slightly by α,β‐methylene‐ATP. Our results suggest that both cholinergic and noradrenergic axon terminals are equipped with P 2 receptors through which the stimulation‐evoked release of transmitter can be modulated by ATP in a positive manner. Because α,β‐methylene‐ATP had an effect on it and 2‐methyl‐2‐thio‐ATP was without action, it is suggested that presynaptic P 2x purinoceptors are involved. Therefore, it is concluded that if ATP is coreleased with a transmitter or released from another source, it might exert per se a positive influence on transmitter release evoked by axonal firing. Subsequently, adenosine, its breakdown product, might reduce transmitter release via presynaptic PI receptors.