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

Rubovitch, Vardit; Gafni, Mikhal; Sarne, Yosef

doi:10.1016/s0169-328x(02)00174-2

Cited by 51 publications

(46 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Despite these excellent agreements, however, other reports on the effects of cannabinoids on LTCCs appear controversial. In NG108-15 cells [9] and in lactotroph-derived GH 4 C 1 cell line [17], LTCCs are not affected by WIN 55,212-2 and cannabimimetic agonists up-regulate Ca 2+ influxes through LTCCs in N18TG2 cells via a PTXinsensitive pathway [18].…”

Section: L-type Versus Non-l-type Channel Modulation By Cannabinoidsmentioning

confidence: 91%

L-type channel inhibition by CB1 cannabinoid receptors is mediated by PTX-sensitive G proteins and cAMP/PKA in GT1-7 hypothalamic neurons

et al. 2009

View full text Add to dashboard Cite

a b s t r a c tUsing immortalized hypothalamic GT1-7 neurons, which express the CB1 cannabinoid receptor (CB1R) and three Ca 2+ channel types (T, R and L), we found that the CB1R agonist WIN 55,212-2 inhibited the voltage-gated Ca 2+ currents by about 35%. The inhibition by WIN 55,212-2 (10 M) was reversible and prevented by nifedipine (3 M), suggesting a selective action on L-type Ca 2+ channels (LTCCs). WIN 55,212-2 action exhibited all the features of voltage-independent Ca 2+ channel modulation: (1) no changes of the activation kinetics, (2) equal depressive action at all potentials and (3) no facilitation following strong prepulses. At variance with WIN 55,212-2, the CB1R inverse agonist AM-251 (10 M) caused 20% increase of Ca 2+ currents. The inhibition of LTCCs by WIN 55,212-2 was prevented by overnight PTX-incubation and by intracellular perfusion with GDP-␤-S. The latter caused also a 20% Ca 2+ current up-regulation. WIN 55,212-2 action was also prevented by application of the PKA-blocker H89 or by loading the neurons with 8-CPT-cAMP. Our results suggest that LTCCs in GT1-7 neurons are partially inhibited at rest due to a constitutive CB1R activity removed by AM-251 and GDP-␤-S. Activation of CB1R via PTX-sensitive G proteins and cAMP/PKA pathway selectively depresses LTCCs that critically control the synchronized spontaneous firing and pulsatile release of gonadotropin-releasing hormone in GT1-7 neurons.

show abstract

Section: L-type Versus Non-l-type Channel Modulation By Cannabinoidsmentioning

confidence: 91%

L-type channel inhibition by CB1 cannabinoid receptors is mediated by PTX-sensitive G proteins and cAMP/PKA in GT1-7 hypothalamic neurons

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Inhibition of L-type calcium channels by cannabinoid stimulation was detected in cerebral vessels (Gebremedhin et al 1999), in retinal bipolar cells (Straiker et al 1999) and in neonatal rat solitary tract cells (Endoh 2006), whereas activation of these channels was reported in N18TG2 cells (Rubovitch et al 2002). Inhibition of N-type calcium channels was detected in a number of experiments (Caulfield & Brown 1992, Mackie & Hille 1992, Felder et al 1993, Mackie et al 1993, Pan et al 1996, Brown et al 2004, Azad et al 2008, and this effect may have a role in the presynaptic inhibition and retrograde signalling induced by cannabinoids (Freund et al 2003, Howlett 2005.…”

Section: Modulation Of Ion Channelsmentioning

confidence: 99%

Signal transduction of the CB1 cannabinoid receptor

Turu

Hunyady

2009

Journal of Molecular Endocrinology

282

218

View full text Add to dashboard Cite

The CB 1 cannabinoid receptor (CB 1 R) is the major cannabinoid receptor in neuronal cells and the brain, but it also occurs in endocrine cells and other peripheral tissues. CB 1 R is a member of the superfamily of G-protein-coupled receptors (GPCRs), which are characterized by seven transmembrane helices. The major mediators of CB 1 R are the G proteins of the G i/o family, which inhibit adenylyl cyclases in most tissues and cells, and regulate ion channels, including calcium and potassium ion channels. Regulation of ion channels is an important component of neurotransmission modulation by endogenous cannabinoid compounds released in response to depolarization and Ca 2C -mobilizing hormones. However, evidence exists that CB 1 Rs can also stimulate adenylyl cyclase via G s , induce receptor-mediated Ca 2C fluxes and stimulate phospholipases in some experimental models. Stimulation of CB 1 R also leads to phosphorylation and activation of mitogen-activated protein kinases (MAPK), such as p42/p44 MAPK, p38 MAPK and c-Jun N-terminal kinase, which can regulate nuclear transcription factors. Activated and phosphorylated CB 1 Rs also associate with b-arrestin molecules, which can induce the formation of signalling complexes and participate in the regulation of GPCR signalling. Recent data also suggest that CB 1 Rs can form homo-and heterodimers/oligomers, and the altered pharmacological properties of these receptor complexes may explain the pharmacological differences observed in various tissues.

show abstract

“…Furthermore, ultrastructural analysis of the corpus callosum revealed more myelinated axons following 3 weeks of CPZ diet combined with 0.5 mg/kg, but not in those mice treated with 1 mg/kg. In fact, many studies have demonstrated either therapeutic or deleterious effects of cannabinoids on the viability of various cell types (for review, see 23 that might be attributable to blockage or stimulation of calcium entry into the cell, which in turn depends on cannabinoid concentration 24.…”

Section: Discussionmentioning

confidence: 99%

The Cannabinoid CB1/CB2 Agonist WIN55212.2 Promotes Oligodendrocyte Differentiation In Vitro and Neuroprotection During the Cuprizone‐Induced Central Nervous System Demyelination

et al. 2016

View full text Add to dashboard Cite

SummaryAim and methodsDifferent types of insults to the CNS lead to axon demyelination. Remyelination occurs when the CNS attempts to recover from myelin loss and requires the activation of oligodendrocyte precursor cells. With the rationale that CB1 receptor is expressed in oligodendrocytes and marijuana consumption alters CNS myelination, we study the effects of the cannabinoid agonist WIN55212.2 in (1) an in vitro model of oligodendrocyte differentiation and (2) the cuprizone model for demyelination.ResultsThe synthetic cannabinoid agonist WIN55212.2 at 1 μM increased the myelin basic protein mRNA and protein expression in vitro. During cuprizone‐induced acute demyelination, the administration of 0.5 mg/kg WIN55212.2 confers more myelinated axons, increased the expression of retinoid X receptor alpha, and declined nogo receptor expression. Controversially, 1 mg/kg of the drug increased the number of demyelinated axons and reduced the expression of nerve growth factor inducible, calreticulin and myelin‐related genes coupling specifically with a decrease in 2′,3′‐cyclic nucleotide 3′ phosphodiesterase expression.ConclusionThe cannabinoid agonist WIN55212.2 promotes oligodendrocyte differentiation in vitro. Moreover, 0.5 mg/kg of the drug confers neuroprotection during cuprizone‐induced demyelination, while 1 mg/kg aggravates the demyelination process.

show abstract

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

Cited by 51 publications

References 22 publications

L-type channel inhibition by CB1 cannabinoid receptors is mediated by PTX-sensitive G proteins and cAMP/PKA in GT1-7 hypothalamic neurons

L-type channel inhibition by CB1 cannabinoid receptors is mediated by PTX-sensitive G proteins and cAMP/PKA in GT1-7 hypothalamic neurons

Signal transduction of the CB1 cannabinoid receptor

The Cannabinoid CB1/CB2 Agonist WIN55212.2 Promotes Oligodendrocyte Differentiation In Vitro and Neuroprotection During the Cuprizone‐Induced Central Nervous System Demyelination

Contact Info

Product

Resources

About