Diazepam inhibits calcium, calmodulin-dependent protein kinase in primary astorcyte cultures

E. Babcock-Atkinson, L. O.B. Norenberg, M. D. Norenberg, J. T. Neary

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Abstract

The effect of the anticonvulsants diazepam, phenytoin, and valproic acid on calcium, calmodulin-dependent protein phosphorylation in astrocytes was investigated. We found that diazepam inhibited calcium, calmodulin-stimulated phosphorylation in both supernatant and membrane fractions from primary cultures of rat astrocytes, whereas phenytoin and valproic acid (50-500 μM) had little to no effect. Phosphate incorporation in several protein bands, including the major substrates of 59 and 53 kDa, was inhibited by diazepam. A decrease in phosphate incorporation in these crude preparations was observed at 25 μM diazepam and 50% inhibition was attained at about 100 μM. Dibutyryl cyclic AMP-treated astrocytes were enriched in the 59 kDa phosphoprotein; this band was particularly sensitive to diazepam in these cells. These results indicate that diazepam is capable of inhibiting calcium, calmodulin-dependent protein kinase activity in astrocytes, thereby suggesting a possible site of diazepam action and a potential mechanism for a role of astrocytes in epileptogenesis.

Original languageEnglish (US)
Pages (from-to)399-403
Number of pages5
JournalBrain Research
Volume484
Issue number1-2
DOIs
StatePublished - Apr 10 1989

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Keywords

  • Anticonvulsant
  • Astrocyte
  • Calcium
  • Calmodulin kinase
  • Diazepam
  • Epilepsy
  • Protein phosphorylation

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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