Methylcobalamin induces a long-lasting enhancement of the field potential in rat suprachiasmatic nucleus slices.
Optic nerve stimulation has been reported to evoke a field potential (FP) in rat suprachiasmatic nucleus (SCN) slices. Methylcobalamin,delta-(5,6-dymethylbenzimidazolyl)-Co-methyl-cobam ide (Me-B12) enhanced this FP and the enhancement lasted more than 1 h after washing out. Maximal enhancement (143.6 +/- 9.8%) was achieved at a concentration of 10 microM. By contrast, cyanocobalamin containing CN- instead of CH3- showed no enhancement of the amplitude in the FP. Me-B12 induced enhancement of FP was strongly blocked by an N-methyl-D-aspartate (NMDA) receptor antagonist, DL-2-amino-5-phosphonovaleric acid (APV). These results indicate that CH3- in the Me-B12 is required to modulate the FP amplitude and the NMDA receptor is involved in the long-lasting FP enhancement induced by Me-B12. The present results suggest that Me-B12 modifies the photic entrainment of the circadian clock in the suprachiasmatic nucleus via an activation of NMDA receptors.
Nishikawa
Y
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Shibata
S
S
Shimazoe
T
T
Watanabe
S
S
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D009900:Optic Nerve / Q000502:physiology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013268:Stimulation, Chemical; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000502:physiology*; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; C019476:mecobalamin; D014805:Vitamin B 12