title: Muscarinic depression of excitatory synaptic transmission mediated by the presynaptic M3 receptors in the rat neostriatum.
abstract: The effect of carbachol on the excitatory synaptic transmission was studied in rat neostriatal neurons using intracellular and whole-cell voltage clamp-recording methods. Depolarizing excitatory postsynaptic potentials (EPSPs) were evoked by cortical stimulation. Superfusion of carbachol (0.01-3 microM) reversibly decreases the EPSP amplitude in a concentration-dependent manner and with an estimated IC50 of 0.3 microM. While, neither the N-methyl-D-aspartate (NMDA, 100 microM)- nor (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA, 100 microM)-induced response was affected by carbachol (0.1 microM). In addition, the inhibitory effect induced by carbachol at a low concentration of 0.1 microM was attenuated by 4-diphenylacetoxy-N,N-methyl-piperidine (4-DAMP), a selective M3 muscarinic receptor antagonist. However, other muscarinic subtype (M1 or M2) antagonists could also block the inhibitory effect by carbachol 0.1 microM. The rank order of antagonist potency was: 4-DAMP (M3 antagonist) > methoctramine (M2 antagonist) > pirenzepine (M1 antagonist). Based on these findings, we conclude that carbachol at a low concentration (< or = 0.1 microM) reduced the excitatory response of neostriatal neurons following cortical stimulation via presynaptic M3 muscarinic receptors located on the terminals of corticostriatal neurons.
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan, Taiwan, Republic of China.
authors.forename: K S
authors.initials: KS
authors.lastname: Hsu
authors.forename: C C
authors.initials: CC
authors.lastname: Huang
authors.forename: P W
authors.initials: PW
authors.lastname: Gean
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D003864:Depression, Chemical; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D016202:N-Methylaspartate / Q000494:pharmacology; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects*; D017661:Receptors, Presynaptic / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D010880:Piperidines; D011976:Receptors, Muscarinic; D017661:Receptors, Presynaptic; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D002217:Carbachol