Muscarinic Inhibition of Endogenous Glutamate Release from Rat Hippocampus Synaptosomes

The effects of acetylcholine (ACh) on the depolarization-evoked release of endogenous glutamic acid (Glu) have been studied using synaptosomes prepared from rat hippocampus and depolarized in superfusion with 15 mM KCl. Acetylcholine inhibited Glu release in a concentration-dependent way. The natural agonist was particularly effective causing 50% inhibition of Glu release at 10 microM in the absence of acetylcholinesterase (AChE) inhibitors. The inhibitory effect of ACh on the K+-evoked release of Glu was antagonized by the selective muscarinic receptor antagonist atropine but not by the nicotinic receptor antagonist mecamylamine. The data represent the first demonstration that muscarinic receptors located on Glu axon terminals in rat hippocampus may modulate the release of Glu.