Nicotine protects cultured cortical neurons against glutamate-induced cytotoxicity via alpha7-neuronal receptors and neuronal CNS receptors.
We examined the effects of nicotine on glutamate-induced cytotoxicity using primary cultures of rat cortical neurons. The cell viability decreased significantly when cultures were exposed to glutamate for 10 min and then incubated with glutamate-free medium for 1 h. The exposure of cultures to nicotine (10 microM) for 8-24 h prior to glutamate application ameliorated the glutamate-induced cytotoxicity, with no significant effect of nicotine alone on the cell viability. Neuroprotection by nicotine was dependent on the incubation period. alpha-bungarotoxin (alpha-BTX) and methyllycaconitine (MLA), both of which are alpha7-neuronal receptor antagonists, and dihydro-beta-erythroidine (DHbetaE), a neuronal central nervous system (CNS) receptor antagonist, each significantly antagonized the protection by nicotine against glutamate-induced cytotoxicity. Ionomycin, a calcium ionophore, and S-nitrosocysteine (SNOC), a nitric oxide (NO) donor, also induced cytotoxicity in a manner similar to glutamate. Nicotine protected cultures against ionomycin-induced cytotoxicity, but not against SNOC-induced cytotoxicity. These results suggest that nicotine protects cultured cortical neurons against glutamate-induced cytotoxicity via alpha7-neuronal receptors and neuronal CNS receptors by reducing NO-formation triggered by Ca2+ influx.
Kaneko
S
S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Maeda
T
T
Kume
T
T
Kochiyama
H
H
Akaike
A
A
Shimohama
S
S
Kimura
J
J
D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000633:toxicity; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity*; D015759:Ionomycin / Q000037:antagonists & inhibitors / Q000633:toxicity; D007476:Ionophores / Q000037:antagonists & inhibitors / Q000633:toxicity; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects*; D026403:S-Nitrosothiols; D014118:Toxins, Biological / Q000494:pharmacology
D002038:Bungarotoxins; D018691:Excitatory Amino Acid Antagonists; D007476:Ionophores; D018696:Neuroprotective Agents; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D026403:S-Nitrosothiols; D014118:Toxins, Biological; C054634:methyllycaconitine; D004079:Dihydro-beta-Erythroidine; D018698:Glutamic Acid; D015759:Ionomycin; D009538:Nicotine; C021315:S-nitrosocysteine; D003545:Cysteine; D000157:Aconitine