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