Muscarinic receptors mediate direct inhibition of GABA release from rat striatal nerve terminals.
The effects of acetylcholine (ACh) on the depolarization-evoked release of [3H]gamma-aminobutyric acid ([3H]GABA) have been investigated using synaptosomes prepared from rat corpus striatum and depolarized by superfusion with 9 mM KCl. Acetylcholine inhibited the [3H]GABA overflow in a concentration-dependent manner. The maximal effect was about 50%. The IC50 value (concentration producing half-maximal effect) amounted to 1 microM, in the absence of acetylcholinesterase inhibitors. The effect of ACh on the K(+)-evoked [3H]GABA release was counteracted by the muscarinic receptor antagonist atropine, but not by the nicotinic receptor antagonist mecamylamine or by the selective M1 antagonist pirenzepine. The data show that muscarinic receptors with low affinity for pirenzepine are localized on GABAergic nerve endings in rat corpus striatum where they may directly inhibit the release of GABA.
Marchi
M
M
Istituto di Farmacologia e Farmacognosia, Università degli Studi di Genova, Italy.
Sanguineti
P
P
Raiteri
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D018756:GABA Antagonists; D008297:Male; D009411:Nerve Endings / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018756:GABA Antagonists; D011976:Receptors, Muscarinic; D005680:gamma-Aminobutyric Acid; D000109:Acetylcholine