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 language | English |
|---|---|
| Pages (from-to) | 113-119 |
| Number of pages | 7 |
| Journal | European Journal of Pharmacology |
| Volume | 221 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1992 Oct 6 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Effect of muscarinic cholinergic drugs on ischemia-induced decreases in glucose uptake and CA1 field potentials in rat hippocampus slices
AU - Shibata, Shigenobu
AU - Koutaroh, Kodama
AU - Keiko, Tominaga
AU - Takeshi, Tanaka
AU - Shigenori, Watanabe
PY - 1992/10/6
Y1 - 1992/10/6
N2 - 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.
AB - 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.
KW - (In vitro)
KW - 2-Deoxyglucose uptake
KW - CA1 field potentials
KW - Cholinergic drugs
KW - Hippocampus
KW - Hypoxia/hypoglycemia
UR - http://www.scopus.com/inward/record.url?scp=0026646275&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026646275&partnerID=8YFLogxK
U2 - 10.1016/0014-2999(92)90779-4
DO - 10.1016/0014-2999(92)90779-4
M3 - Article
C2 - 1459186
AN - SCOPUS:0026646275
VL - 221
SP - 113
EP - 119
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1
ER -