Effect of muscarinic cholinergic drugs on ischemia-induced decreases in glucose uptake and CA1 field potentials in rat hippocampus slices

Shigenobu Shibata, Kodama Koutaroh, Tominaga Keiko, Tanaka Takeshi, Watanabe Shigenori

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

To clarify the role of muscarinic acetylcholinc receptors in the hypoxia/ hypoglycemia (ischemia)-induced functional deficit in hippocampal neurons, we examined the effect of cholinergic drugs on ischemia-induced impairments of glucose uptake and CA1 field potentials in hippocampus slices. Muscarinic receptors were subdivided into M1 (high affinity for pirenzepine) and M1 (low affinity for pirenzcpine) subtypes. The M1 receptor subtype is coupled to an increase in phosphoinositide hydrolysis and the M2 receptor subtype is associated with inhibition of adenylate cyclase. The greater potency of carbachol in stimulating phosphoinositide hydrolysis resulted in exacerbated ischemia-induced deficits. Treatment with the muscarinic receptor antagonists scopolamine and pircnzepine (M1 receptor-selective antagonist) had a strong dose-dependent protective effect against ischemia-induced deficits. Oxotremorine and McN-A-343, weak stimulators of phosphoinositide hydrolysis and strong inhibitors of adenylate cyclase, had a weak neuroprotective action against ischemia-induced deficits. These results suggest that stimulation of M1 musarinic receptors coupled with an increase in phosphoinositide hydrolysis may play a facilatory role in ischemia-induced deficits. Stimulation of M2 muscarinic receptors may play an inhibitory role in ischemia-induced neuronal deficits.

Original languageEnglish
Pages (from-to)113-119
Number of pages7
JournalEuropean Journal of Pharmacology
Volume221
Issue number1
DOIs
Publication statusPublished - 1992 Oct 6
Externally publishedYes

Fingerprint

Cholinergic Agents
Hippocampus
Ischemia
Glucose
Phosphatidylinositols
Muscarinic Receptors
Hydrolysis
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride
Muscarinic M2 Receptors
Oxotremorine
Pirenzepine
Muscarinic Antagonists
Scopolamine Hydrobromide
Carbachol
Hypoglycemia
Adenylyl Cyclases
Neurons

Keywords

  • (In vitro)
  • 2-Deoxyglucose uptake
  • CA1 field potentials
  • Cholinergic drugs
  • Hippocampus
  • Hypoxia/hypoglycemia

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Effect of muscarinic cholinergic drugs on ischemia-induced decreases in glucose uptake and CA1 field potentials in rat hippocampus slices. / Shibata, Shigenobu; Koutaroh, Kodama; Keiko, Tominaga; Takeshi, Tanaka; Shigenori, Watanabe.

In: European Journal of Pharmacology, Vol. 221, No. 1, 06.10.1992, p. 113-119.

Research output: Contribution to journalArticle

Shibata, Shigenobu ; Koutaroh, Kodama ; Keiko, Tominaga ; Takeshi, Tanaka ; Shigenori, Watanabe. / Effect of muscarinic cholinergic drugs on ischemia-induced decreases in glucose uptake and CA1 field potentials in rat hippocampus slices. In: European Journal of Pharmacology. 1992 ; Vol. 221, No. 1. pp. 113-119.
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