Heterogeneity of muscarinic autoreceptors and heteroreceptors in the rat brain: effects of a novel M1 agonist, AF102B

The effects of oxotremorine and AF102B (cis-2-methylspiro-(1,3-oxathiolane-5,3')-quinuclidine), a novel M1-selective muscarinic agonist, on acetylcholine (ACh) and dopamine (DA) release from superfused rat hippocampal and striatal synaptosomes were investigated. Synaptosomes that had been prela...

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Bibliographic Details
Published inEuropean journal of pharmacology Vol. 155; no. 1-2; p. 77
Main Authors Ono, S, Saito, Y, Ohgane, N, Kawanishi, G, Mizobe, F
Format Journal Article
LanguageEnglish
Published Netherlands 11.10.1988
Subjects
Acetylcholine - metabolism
Animals
Brain Chemistry
Corpus Striatum - drug effects
Corpus Striatum - metabolism
Dopamine - metabolism
Hippocampus - drug effects
Hippocampus - metabolism
In Vitro Techniques
Male
Oxotremorine - antagonists & inhibitors
Oxotremorine - pharmacology
Parasympathomimetics - pharmacology
Pirenzepine - pharmacology
Potassium - pharmacology
Quinuclidines - pharmacology
Rats
Rats, Inbred Strains
Receptors, Muscarinic - metabolism
Synaptosomes - drug effects
Synaptosomes - metabolism
Thiophenes
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Summary:The effects of oxotremorine and AF102B (cis-2-methylspiro-(1,3-oxathiolane-5,3')-quinuclidine), a novel M1-selective muscarinic agonist, on acetylcholine (ACh) and dopamine (DA) release from superfused rat hippocampal and striatal synaptosomes were investigated. Synaptosomes that had been prelabeled with [3H]choline or [3H]DA were depolarized by high K+. Oxotremorine and AF102B decreased the K+-evoked [3H]ACh release from hippocampal synaptosomes and increased the K+-evoked [3H]DA release from striatal synaptosomes. The dose-response curves showed that AF102B was far less potent than oxotremorine at the hippocampal presynaptic muscarinic receptors (autoreceptors). On the other hand, AF102B was more potent than oxotremorine at the muscarinic receptors on the striatal dopaminergic terminals (heteroreceptors). Pirenzepine, a selective M1 antagonist, counteracted the effects of oxotremorine on [3H]DA release more potently than it did the effects of oxotremorine on [3H]ACh release. Our results suggest that AF102B and pirenzepine discriminate pharmacologically between muscarinic autoreceptors and heteroreceptors.
ISSN:0014-2999
DOI:10.1016/0014-2999(88)90404-9