Endogenous aspartate release in the rat hippocampus is inhibited by M2 'cardiac' muscarinic receptors.
The release of endogenous aspartic acid elicited by depolarization of rat hippocampus synaptosomes with 15 mM KCl was totally calcium-dependent. Acetylcholine (ACh) added to the superfusion medium inhibited the K(+)-evoked release of aspartate in a concentration-dependent manner. The effect of ACh was mimicked by oxotremorine and carbachol. It was insensitive to the nicotinic receptor antagonist mecamylamine but blocked by the non-selective muscarinic receptor antagonist atropine. Further pharmacological characterization of the muscarinic receptor involved showed that the ACh effects was insensitive to the M1 selective muscarinic receptor antagonists pirenzepine and dicyclomine. However, the inhibition by ACh of aspartate release was counteracted by 11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H- pyrido-[2-3-b][1,4]benzodiazepine-6-one (AF-DX 116), a selective M2 'cardiac' receptor antagonist. The calcium dependence of the release of aspartate and its regulation through presynaptic receptors are suggestive of a transmitter role for this excitatory amino acid. Moreover, the similarities between the present results and those previously obtained with glutamate are compatible with the idea that aspartate and glutamate are co-released in the rat hippocampus.
Raiteri
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Istituto di Farmacologia e Farmacognosia, Università degli Studi di Genova, Italy.
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D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D002118:Calcium / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006321:Heart / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D009467:Neuromuscular Depolarizing Agents; D011976:Receptors, Muscarinic; D001224:Aspartic Acid; D010890:Pirenzepine; D010095:Oxotremorine; D002217:Carbachol; D000109:Acetylcholine; C048593:otenzepad; D011188:Potassium; D002118:Calcium