1. The mechanism of the inhibitory action of presynaptic muscarinic receptors on the release of acetylcholine from striatal cholinergic neurons is not known. We investigated how the electrically stimulated release of [3H]-acetylcholine from superfused rat striatal slices and its inhibition by carbachol are affected by specific inhibitors of voltage-operated calcium channels of the L-type (nifedipine), N-type (omega-conotoxin GVIA) and P/Q-type (omega-agatoxin IVA). 2. The evoked release of [3H]-acetylcholine was not diminished by nifedipine but was lowered by omega-conotoxin GVIA and by omega-agatoxin IVA, indicating that both the N- and the P/Q-type (but not the L-type) channels are involved in the release. The N-type channels were responsible for approximately two thirds of the release. The release was >97% blocked when both omega-toxins acted together. 3. The inhibition of [3H]-acetylcholine release by carbachol was not substantially affected by the blockade of the L- or P/Q-type channels. It was diminished but not eliminated by the blockade of the N-type channels. 4. In experiments on slices in which cholinesterases had been inhibited by paraoxon, inhibition of [3H]-acetylcholine release by endogenous acetylcholine accumulating in the tissue could be demonstrated by the enhancement of the release after the addition of atropine. The inhibition was higher in slices with functional N-type than with functional P/Q-type channels. 5. We conclude that both the N- and the P/Q-type calcium channels contribute to the stimulation-evoked release of acetylcholine in rat striatum, that the quantitative contribution of the N-type channels is higher, and that the inhibitory muscarinic receptors are more closely coupled with the N-type than with the P/Q-type calcium channels.

• MeSH
• Acetylcholine metabolism   MeSH
• Muscarinic Agonists pharmacology   MeSH
• Dopamine Antagonists pharmacology   MeSH
• Muscarinic Antagonists pharmacology   MeSH
• Atropine pharmacology   MeSH
• Calcium Channel Blockers pharmacology   MeSH
• Cholinesterase Inhibitors pharmacology   MeSH
• Domperidone pharmacology   MeSH
• Haloperidol pharmacology   MeSH
• Carbachol pharmacology   MeSH
• Rats MeSH
• Neostriatum drug effects   metabolism   MeSH
• omega-Agatoxin IVA MeSH
• omega-Conotoxin GVIA MeSH
• Paraoxon pharmacology   MeSH
• Spider Venoms pharmacology   MeSH
• Peptides pharmacology   MeSH
• Receptors, Muscarinic drug effects   metabolism   MeSH
• Receptors, Presynaptic drug effects   metabolism   MeSH
• In Vitro Techniques MeSH
• Calcium Channels drug effects   metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Names of Substances
• Acetylcholine MeSH
• Muscarinic Agonists MeSH
• Dopamine Antagonists MeSH
• Muscarinic Antagonists MeSH
• Atropine MeSH
• Calcium Channel Blockers MeSH
• Cholinesterase Inhibitors MeSH
• Domperidone MeSH
• Haloperidol MeSH
• Carbachol MeSH
• omega-Agatoxin IVA MeSH
• omega-Conotoxin GVIA MeSH
• Paraoxon MeSH
• Spider Venoms MeSH
• Peptides MeSH
• Receptors, Muscarinic MeSH
• Receptors, Presynaptic MeSH
• Calcium Channels MeSH