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Effect of calmodulin antagonists on phospholipase D activity in SH-SY5Y cells.

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Author

  • María del Carmen Boyano-Adánez
  • Lena Gustavsson

Summary, in English

The aim of this study was to investigate the involvement of calmodulin in phospholipase D activation in SH-SY5Y cells. Cells prelabelled with [3H]-palmitic acid were incubated with calmodulin antagonists and/or other compounds. Phosphatidylethanol, a specific marker for phospholipase D activity, and phosphatidic acid were analysed. The calmodulin antagonists, calmidazolium and trifluoperazine, induced an extensive increase in phosphatidylethanol formation, and thus increased basal phospholipase D activity, in a dose- and time-dependent manner. The effect of calmidazolium on carbachol-induced activation of muscarinic receptors was also studied. Calmidazolium did not significantly affect the amount of phosphatidylethanol formed following carbachol addition. However, taking into account the increase in basal activity observed after calmidazolium addition, calmidazolium probably inhibits the muscarinic receptor-induced phospholipase D activation. In addition to phosphatidylethanol, basal phosphatidic acid levels were also increased after calmidazolium and trifluoperazine addition. Incubation with calmidazolium (10 microM) for 10 min induced a two-fold increase in phosphatidic acid. The calmidazolium-induced increase in basal phospholipase D activity was not affected by the protein kinase inhibitors H7 and staurosporine. On the other hand tyrosine kinase inhibitors abolished the calmidazolium-induced activation of phospholipase D. Calmidazolium also induced tyrosine phosphorylation in parallel to the phospholipase D activation. In conclusion, our data indicate that calmodulin antagonists induce phospholipase D activity in SH-SY5Y cells via a tyrosine kinase dependent pathway. This may point to a negative control of phospholipase D by calmodulin although a calmodulin-independent mechanism cannot be excluded. Calmodulin antagonists may be useful tools to further elucidate the mechanisms of phospholipase D regulation.

Publishing year

2002

Language

English

Pages

261-268

Publication/Series

Neurochemistry International

Volume

40

Issue

3

Document type

Journal article

Publisher

Elsevier

Topic

  • Pharmacology and Toxicology
  • Medicinal Chemistry
  • Neurology

Keywords

  • Protein Kinase C : antagonists & inhibitors
  • Phosphorylation : drug effects
  • Protein-Tyrosine Kinase : antagonists & inhibitors
  • Tyrosine : metabolism
  • Support Non-U.S. Gov't
  • Trifluoperazine : administration & dosage : pharmacology
  • Dose-Response Relationship Drug
  • Enzyme Inhibitors : pharmacology
  • Cholinergic Agonists : pharmacology
  • Calmodulin : antagonists & inhibitors
  • Carbachol : pharmacology
  • Cell Line
  • Imidazoles : administration & dosage : pharmacology
  • Glycerophospholipids : metabolism
  • Phospholipase D : metabolism
  • Phosphatidic Acids : metabolism

Status

Published

ISBN/ISSN/Other

  • ISSN: 0197-0186