Transient increase of cyclic AMP induced by glutamate in cultured neurons from rat spinal cord.
We demonstrated that glutamate increased the cyclic AMP level in cultured neurons from rat spinal cord. A bath application of glutamate (300 microM) elicited a rapid increase of the cyclic AMP concentration reaching a level three times as high as the basal level in approximately 3 min, and its content then decreased to the control level in 15 min. The increase was not observed in a Ca(2+)-free medium and was inhibited by an antagonist of NMDA receptors or a voltage-sensitive Ca2+ channel blocker. Preincubation with W7 also inhibited the glutamate-evoked cyclic AMP increase. NMDA, aspartate, and high-K+ conditions also induced a cyclic AMP increase; however, a decreasing phase did not follow. The decreasing phase was observed when (2S,1'S,2'S)-2-(carboxycyclopropyl)-glycine, a potent agonist for metabotropic glutamate receptors, was combined with NMDA. These results suggest that the cyclic AMP increase is mediated by a Ca2+ influx via both NMDA receptors and voltage-sensitive Ca2+ channels followed by an activation of the Ca2+/calmodulin system, and the decreasing phase observed in the case of glutamate exposure is due to the activation of the metabotropic glutamate receptors.
Tsuji
K
K
Department of Physiology, Ehime University School of Medicine, Japan.
Nakamura
Y
Y
Ogata
T
T
Shibata
T
T
Kataoka
K
K
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors
D002147:Calmodulin; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; D013449:Sulfonamides; D018698:Glutamic Acid; C017967:W 7; D000242:Cyclic AMP; D002118:Calcium