A quantitative pharmacological study of the cholinergic depolarization of hippocampal pyramidal cells in rat brain slices.
Intracellular recordings were performed in rat brain slices and the pharmacology of the depolarizing effect of cholinomimetic drugs on hippocampus CA1 pyramidal cells was quantitatively investigated. Acetylcholine (ACh) and muscarine induced a concentration-dependent depolarization of these cells. The EC50 values were respectively 159 +/- 54 microM and 0.7 +/- 0.15 microM. Physostigmine (1 microM) or tacrine (1 microM) induced a marked shift in the concentration-response curve for ACh. Both drugs were equipotent in this respect. The EC50 values for ACh became, respectively, 2.4 +/- 1.5 microM and 3 +/- 0.9 microM. The depolarizing effect of ACh was completely blocked by atropine, confirming the involvement of a receptor of the muscarinic type. In order to determine the subtype of muscarinic receptor involved, the EC50 values of muscarine were determined in the presence of atropine (100 nM), pirenzepine (1 microM) or AFDX116 (10 microM). The deduced pKB for the antagonists were, respectively, 8.9, 7.4 and 6.5. Comparison with binding data suggests that M1 receptors play a prominent role in the depolarizing effect of cholinomimetic drugs on CA1 pyramidal cells.
Laboratory of Pharmacology, University of Liège, Sart-Tilman, Belgium.
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Scuvée-Moreau
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Seutin
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Dresse
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D016015:Logistic Models; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009116:Muscarine / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D018678:Cholinergic Agents; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D001285:Atropine; D009116:Muscarine; D000109:Acetylcholine