Cholecystokinin-induced protection of cultured cortical neurons against glutamate neurotoxicity.
The effects of cholecystokinin (CCK) on glutamate-induced neurotoxicity were examined using cultured rat cortical neurons. Brief exposure of glutamate followed by an incubation with normal solution for more than 60 min reduced cell viability by 60-70%, compared with control values. Glutamate-induced neurotoxicity was significantly inhibited by MK-801 and ketamine, which are non-competitive blockers of N-methyl-D-aspartate (NMDA) receptors. Octapeptide CCK-8S and CCK-related decapeptide ceruletide at concentrations of 10(-9)-10(-7) M dose-dependently reduced glutamate-induced neurotoxicity. A desulfated analog CCK-8NS, which acts selectively as an antagonist of CCKB receptors, also reduced glutamate neurotoxicity. The neuroprotective effects of CCK were antagonized by L-365260, a CCKB receptor antagonist, but not by L-364718, a CCKA receptor antagonist. These results suggest that CCK protects cortical neurons against NMDA receptor-mediated glutamate neurotoxicity via CCKB receptors.
2nd Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Japan.
A
A
Akaike
Y
Y
Tamura
Y
Y
Sato
K
K
Ozaki
R
R
Matsuoka
S
S
Miura
T
T
Yoshinaga
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D002108:Ceruletide / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020109:Devazepide; D018691:Excitatory Amino Acid Antagonists; D005260:Female; D005971:Glutamates / Q000633:toxicity; D018698:Glutamic Acid; D009474:Neurons / Q000187:drug effects*; D010671:Phenylurea Compounds; D011247:Pregnancy; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D014343:Trypan Blue
D001570:Benzodiazepinones; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; D016194:Receptors, N-Methyl-D-Aspartate; C058121:L 365260; D018698:Glutamic Acid; D002108:Ceruletide; D002766:Cholecystokinin; D014343:Trypan Blue; D020109:Devazepide