1: J Neurochem. 2007 Sep;102(6):1996-2007. Epub 2007 Jun 1.

Agonist selective modulation of tyrosine hydroxylase expression by cannabinoid
ligands in a murine neuroblastoma cell line.

Bosier B, Tilleux S, Najimi M, Lambert DM, Hermans E.

Unité de Chimie Pharmaceutique et de Radiopharmacie (UCL 7340), Université
catholique de Louvain, Brussels, Belgium.

Functional interactions between catecholamines and cannabinoid transmission
systems could explain the influence of Delta(9)-tetrahydrocannabinol on several
central activities. Hence, the presence of cannabinoid CB(1) receptors in
tyrosine hydroxylase (TH) containing cells has been suggested, providing clue for
a direct control of catecholamines synthesis. In the present study, we evidenced 
the constitutive expression of functional cannabinoid CB(1) receptors in N1E-115 
neuroblastoma and reported on the use of this model to examine the influence of
diverse cannabinoid ligands on TH expression. Exposure of the cells to the
high-affinity agonist HU 210 (5 h) resulted in a significant decrease in TH
content (pEC(50): 6.40). In contrast, no change was observed after a similar
treatment with the structurally unrelated agonist CP 55,940. Besides, the use of 
a luciferase reporter assay revealed that these two agonists showed opposite
influences on TH gene promoter activity. Thus, in cells expressing pTH-luc
constructs, inhibition and induction of luciferase activity were respectively
observed with HU 210 (pEC(50): 8.95) and CP 55,940 (pEC(50): 9.09).
Pharmacological characterisation revealed that these reciprocal responses were
both related to the specific activation of cannabinoid CB(1) receptor, suggesting
an agonist-dependent modulation of distinct signalling pathways. While these data
points out the possible pharmacological manipulation of TH expression by
cannabinoid ligands, such approach should take into account the existence of
agonist selective trafficking of cannabinoid CB(1) receptor signalling.

PMID: 17540007 [PubMed - in process]

Related Links

    Cannabinoid CB(1) receptors colocalize with tyrosine hydroxylase in cultured
fetal mesencephalic neurons and their activation increases the levels of this
enzyme. [Brain Res. 2000] PMID:10700552

    CB1 cannabinoid receptor-mediated neurite remodeling in mouse neuroblastoma
N1E-115 cells. [J Neurosci Res. 2001] PMID:11494371

    Pharmacological characterisation of cannabinoid CB(1) receptors in the rat and
mouse. [Eur J Pharmacol. 2000] PMID:10720647

    Identification of WIN55212-3 as a competitive neutral antagonist of the human
cannabinoid CB2 receptor. [Br J Pharmacol. 2005] PMID:15852035

    Cannabinoid CB(1) receptor expression, activation and detection of endogenous
ligand in trabecular meshwork and ciliary process tissues. [Eur J Pharmacol.
2001] PMID:11730719