The cannabinoid agonist DALN positively modulates L-type voltage-dependent calcium-channels in N18TG2 neuroblastoma cells

Vardit Rubovitch, Mikhal Gafni, Yosef Sarne

Research output: Contribution to journalArticlepeer-review

Abstract

The present study demonstrates a novel stimulatory effect of a cannabinoid agonist on calcium channels. DALN (1 nM) potentiated 45Ca2+-uptake by N18TG2 neuroblastoma cells, an effect that was abolished by the specific CB1 receptor antagonist SR141716A. The stimulation of 45Ca2+-uptake by DALN was resistant to pertussis toxin (PTX), suggesting that Gi/Go GTP-binding proteins did not mediate this effect. Furthermore, PTX unmasked a stimulatory effect of a high concentration of DALN (1 μM), which by itself failed to stimulate calcium uptake in naive cells. The stimulatory effect of DALN on calcium entry to the cells was blocked by nicardipine but not by ω-conotoxin GVIA, indicating the entry of calcium through L-type voltage-dependent calcium channels. Blocking cAMP-dependent protein kinase (PKA) by H-89 completely eliminated the elevation in calcium uptake, while blocking protein kinase C (PKC) by chelerythrine and calphostine-C only partially attenuated the stimulation. Blocking calmodulin by W-7 revealed a similar partial inhibition of the stimulatory effect of DALN. Hence, we suggest a cannabinoid-specific, PTX-insensitive, stimulatory effect on L-type voltage-dependent calcium channels, which is mediated by PKA and modulated by PKC and calmodulin.

Original languageEnglish
Pages (from-to)93-102
Number of pages10
JournalMolecular Brain Research
Volume101
Issue number1-2
DOIs
StatePublished - 30 May 2002

Keywords

  • 45Ca
  • Cannabinoid receptor
  • Cannabinoids
  • N18TG2 neuroblastoma cells
  • Voltage-dependent calcium channels

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