Neuroprotective effect of cholecystokininB receptor antagonist on ischemia-induced decrease in CA1 presynaptic fiber spikes in rat hippocampal slices

Yoshitsugu Minamoto, Takeshi Tanaka, Shigenobu Shibata, Shigenori Watanabe

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The effects of cholecystokinin (CCK) receptor agonists and antagonists on hypoxia/hypoglycemia (ischemia)-induced decrease in CA1 presynaptic fiber spikes elicited by the stimulation of Schaffer collaterals were investigated using rat hippocampal slices. Treatment with the CCKB receptor agonist CCK tetrapeptide (CCK4, 0.01-10 μM) exacerbated the ischemia-induced decrease in the CA1 presynaptic potential in a concentration-dependent manner. Whereas, treatment with the CCKB receptor antagonist [(3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-N1-(3-methylphenyl)-urea] (L365260), and not with CCKA receptor antagonist [(3S(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-1H-indole-2-carboxamide] (L364718), produced a concentration-dependent attenuation of the ischemia-induced decrease. The magnitude of recovery of the CA1 field potentials in L365260-treated groups at 10 and 100 nM was 34% and 45%, respectively. The neuroprotective effect of L365260 (0.01 and 0.1 μM) was completely blocked by co-treatment with CCK4 (0.1 μM), a concentration that did not affect the decreased presynaptic potential induced by ischemia. These results demonstrated that the stimulation of the CCKB receptor played a detrimental role in the development of ischemic damage, whereas the blockade of CCKB receptors played a neuroprotective role in ischemic damage, suggesting a facilitatory role of CCK receptor-operated function in ischemia-induced neuronal deficits.

Original languageEnglish
Pages (from-to)81-84
Number of pages4
JournalNeuroscience Letters
Volume167
Issue number1-2
DOIs
Publication statusPublished - 1994 Feb 14
Externally publishedYes

Keywords

  • CA1 presynaptic potential
  • Cholecystokinin
  • Cholecystokinin receptor
  • Cholecystokinin receptor
  • Hippocampus
  • Hypoxia/hypoglycemia
  • In vitro
  • Ischemia

ASJC Scopus subject areas

  • Neuroscience(all)

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