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Both A 1 and A 2a Purine Receptors Regulate Striatal Acetylcholine Release
Author(s) -
Brown Susan J.,
James Stephen,
Reddington Martin,
Richardson Peter J.
Publication year - 1990
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.1471-4159.1990.tb08817.x
Subject(s) - acetylcholine , purine , receptor , acetylcholine receptor , neuroscience , chemistry , biology , biochemistry , endocrinology , enzyme
The receptors responsible for the adenosine‐mediated control of acetylcholine release from immunoaffinitypurified rat striatal cholinergic nerve terminals have been characterized. The relative affinities of three analogues for the inhibitory receptor were ( R )‐phenylisopropyladenosine > cyclohexyladenosine > N ‐ethylcarboxamidoadenosine (NECA), with binding being dependent of the presence of Mg 2+ and inhibited by 5′‐guanylylimidodiphosphate [Gpp(NH)p] and adenosine receptor antagonists. Adenosine A 1 receptor agonists inhibited forskolin‐stimulated cholinergic adenylate cyclase activity, with an IC 50 of 0.5 n M for ( R )‐phenylisopropyladenosine and 500 n M for ( S )‐phenylisopropyladenosine. A 1 agonists inhibited acetylcholine release at concentrations approximately 10% of those required to inhibit the cholinergic adenylate cyclase. High concentrations (1 μ M ) of adenosine A 1 agonists were less effective in inhibiting both adenylate cyclase and acetylcholine release, due to the presence of a lower affinity stimulatory A 2 receptor. Blockade of the A 1 receptor with 8‐cyclopentyl‐1,3‐dipropylxanthine revealed a half‐maximal stimulation by NECA of the adenylate cyclase at 10 n M , and of acetylcholine release at approximately 100 n M . NECA‐stimulated adenylate cyclase activity copurified with choline acetyltransferase in the preparation of the cholinergic nerve terminals, suggesting that the striatal A 2 receptor is localized to cholinergic neurones. The possible role of feedback inhibitory and stimulatory receptors on cholinergic nerve terminals is discussed.