Effects of cholecystokinin octapeptide on genetically determined seizure susceptibility.
Utilizing audiogenic seizure-prone P77PMC rats, the effects of cholecystokinin octapeptide (CCK-8) on genetic seizure susceptibility were studied in vivo, in cerebral cortical synaptosomes, and in cortical neuronal cell cultures. The results showed that CCK-8 could decrease seizure susceptibility, and that the K(+)-stimulated release of GABA in cerebral cortex synaptosomes from seizure-prone animals was depressed. The presence of exogenous CCK-8 (10(-7) M) together with elevated K+ (25 mM) causes a higher increased magnitude in GABA release from synaptosomes (enhanced by 100%) and cell cultures (17 days in vitro, increased by 177%) derived from seizure-prone rats than the controls (increased by 42%, in synaptosomes; and 107% in cell cultures). These preliminary results raise the possibility that the developmental abnormalities in modulation effect of CCK-8 on GABA release in central nervous system may play a role causing greater seizure susceptibility in genetic seizure-prone rats. The analysis of the brain tissue level and gene-expression of CCK-8 will be the important step of further investigation.
Wu
X R
XR
Department of Pediatrics, First Teaching Hospital of Beijing Medical University.
Lin
P X
PX
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004198:Disease Susceptibility; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000517:prevention & control*; D012844:Sincalide / Q000494:pharmacology* / Q000627:therapeutic use; D013574:Synaptosomes / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005680:gamma-Aminobutyric Acid; D012844:Sincalide