Abstract.
Cannabinoid CB1 receptors and vanilloid VR1 receptors are co-localized to some extent in sensory neurons of the spinal cord and dorsal root ganglia. In this study, we over-expressed both receptor types in human embryonic kidney (HEK)-293 cells and investigated the effect of the CB1 agonist HU-210 on the VR1-mediated increase in intracellular Ca2+ ([Ca2+]i), a well-known response of the prototypical VR1 agonist capsaicin. After a 5-min pre-treatment, HU-210 (0.1 μM) significantly enhanced the effect of several concentrations of capsaicin on [Ca2+]i in HEK-293 cells over-expressing both rat CB1 and human VR1 (CB1-VR1-HEK cells), but not in cells over-expressing only human VR1 (VR1-HEK cells). This effect was blocked by the CB1 receptor antagonist SR141716A (0.5 μM), and by phosphoinositide-3-kinase and phospholipase C inhibitors. The endogenous agonist of CB1 and VR1 receptors, anandamide, was more efficacious in inducing a VR1-mediated stimulation of [Ca2+]i in CB1-VR1-HEK cells than in VR1-HEK cells, and part of its effect on the former cells was blocked by SR141716A (0.5 μM). Pre-treatment of CB1-VR1-HEK cells with forskolin, an adenylate cyclase activator, enhanced the capsaicin effect on [Ca2+]i. HU-210, which in the same cells inhibits forskolin-induced enhancement of cAMP levels, blocked the stimulatory effect of forskolin on capsaicin. Our data suggest that in cells co-expressing both CB1 and VR1 receptors, pre-treatment with CB1 agonists inhibits or stimulates VR1 gating by capsaicin depending on whether or not cAMP-mediated signalling has been concomitantly activated.
Similar content being viewed by others
Author information
Authors and Affiliations
Additional information
Received 30 December 2002; received after revision 30 January 2003; accepted 4 February 2003
RID="h1"
RID="h1"
RID="*"
ID="h1"H. Hermann and L. De Petrocellis contributed equally to this work.
ID="*"Corresponding author.
Rights and permissions
About this article
Cite this article
Hermann, H., De Petrocellis, L., Bisogno, T. et al. Dual effect of cannabinoid CB1 receptor stimulation on a vanilloid VR1 receptor-mediated response. CMLS, Cell. Mol. Life Sci. 60, 607–616 (2003). https://doi.org/10.1007/s000180300052
Issue Date:
DOI: https://doi.org/10.1007/s000180300052