TY - JOUR
T1 - The cannabinoid agonist DALN positively modulates L-type voltage-dependent calcium-channels in N18TG2 neuroblastoma cells
AU - Rubovitch, Vardit
AU - Gafni, Mikhal
AU - Sarne, Yosef
N1 - Funding Information:
This research was supported by The Chief Scientist of The Israel Ministry of Health (grant #4534) and The Israel Science Foundation founded by the Israel Academy of Sciences and Humanities (grant #184-99). This work was performed in partial fulfillment of the requirements for a Ph.D. degree for Vardit Rubovitch, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
PY - 2002/5/30
Y1 - 2002/5/30
N2 - 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.
AB - 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.
KW - 45Ca
KW - Cannabinoid receptor
KW - Cannabinoids
KW - N18TG2 neuroblastoma cells
KW - Voltage-dependent calcium channels
UR - http://www.scopus.com/inward/record.url?scp=0037198522&partnerID=8YFLogxK
U2 - 10.1016/S0169-328X(02)00174-2
DO - 10.1016/S0169-328X(02)00174-2
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AN - SCOPUS:0037198522
SN - 0169-328X
VL - 101
SP - 93
EP - 102
JO - Molecular Brain Research
JF - Molecular Brain Research
IS - 1-2
ER -
