Macrolide antibiotics protect neurons in culture against the N-methyl-D-aspartate (NMDA) receptor-mediated toxicity of glutamate.
The immunosuppressive macrolide FK-506 has been shown to protect neurons in culture against glutamate excitotoxicity. This effect was attributed to the binding of immunosuppressants to calcineurin-inhibiting immunophilins. We now report that also the non-immunosuppressive macrolide antibiotics protect neurons in culture against NMDA- but not kainate-mediated excitotoxicity. The effect was structure-dependent: larger macrolide rings were more active. Macrolides did not affect the 3-(2-carboxypiperazin-4yl)-propyl-1-phosphonic acid (CPP) binding or the NMDA-mediated calcium influx.
Manev
H
H
FIDIA Research Laboratories, Abano Terme, Italy.
Favaron
M
M
Candeo
P
P
Fadda
E
E
Lipartiti
M
M
Milani
D
D
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000506:poisoning*; D018698:Glutamic Acid; D006098:Granulocytes / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D016559:Tacrolimus / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016559:Tacrolimus