TY - JOUR
T1 - Cannabinoid CB1 receptor elevation of intracellular calcium in neuroblastoma SH-SY5Y cells
T2 - interactions with muscarinic and delta-opioid receptors
AU - Marini, Pietro
AU - Moriello, Aniello Schiano
AU - Cristino, Luigia
AU - Palmery, Maura
AU - De Petrocellis, Luciano
AU - Di Marzo, Vincenzo
PY - 2009/7
Y1 - 2009/7
N2 - Although coupled to Gi/o proteins, cannabinoid CB1 receptors can also activate intracellular Ca2+ ([Ca2+]i) accumulation through not fully understood mechanisms. We report that in, human neuroblastoma SH-SY5Y cells, CB1 activation with the specific agonist arachidonoylchloroethanolamide (ACEA), weakly elevates [Ca2+]i and that this effect, when using low (1–100 nM) concentrations of ACEA, is enhanced by the previous activation of Gq/11-coupled M3 muscarinic receptors with carbachol, dose-dependently and up to ~ 8-fold. A similar behaviour was also observed with carbachol and the Gi/o-coupled d-opioid receptor. Furthermore, stimulation of CB1 receptors produced a concentration-dependent leftward shift of the elevation of [Ca2+]i by d-opioid receptors. These stimulatory effects were variedly attenuated by selective antagonists of each receptor, pertussis toxin, inhibitors of phospholipase C (U73122 and D609), and, when assessed in the presence of extracellular Ca2+, by the block of voltage-activated calcium channels. Cholera toxin only slightly inhibited the Gq/11-Gi/o-mediated cross-talk, but induced a stronger inhibition of the Gi/o-Gi/o-mediated interaction. These findings suggest that activation of M3 muscarinic receptors might produce a qualitative alteration of the signaling associated with Gi/o-coupled receptors, and that sequential activation of CB1 and d-opioid receptors, both coupled to Gi/o, produces instead synergistic effects on [Ca2+]i elevation.
AB - Although coupled to Gi/o proteins, cannabinoid CB1 receptors can also activate intracellular Ca2+ ([Ca2+]i) accumulation through not fully understood mechanisms. We report that in, human neuroblastoma SH-SY5Y cells, CB1 activation with the specific agonist arachidonoylchloroethanolamide (ACEA), weakly elevates [Ca2+]i and that this effect, when using low (1–100 nM) concentrations of ACEA, is enhanced by the previous activation of Gq/11-coupled M3 muscarinic receptors with carbachol, dose-dependently and up to ~ 8-fold. A similar behaviour was also observed with carbachol and the Gi/o-coupled d-opioid receptor. Furthermore, stimulation of CB1 receptors produced a concentration-dependent leftward shift of the elevation of [Ca2+]i by d-opioid receptors. These stimulatory effects were variedly attenuated by selective antagonists of each receptor, pertussis toxin, inhibitors of phospholipase C (U73122 and D609), and, when assessed in the presence of extracellular Ca2+, by the block of voltage-activated calcium channels. Cholera toxin only slightly inhibited the Gq/11-Gi/o-mediated cross-talk, but induced a stronger inhibition of the Gi/o-Gi/o-mediated interaction. These findings suggest that activation of M3 muscarinic receptors might produce a qualitative alteration of the signaling associated with Gi/o-coupled receptors, and that sequential activation of CB1 and d-opioid receptors, both coupled to Gi/o, produces instead synergistic effects on [Ca2+]i elevation.
KW - calcium
KW - cannabinoid
KW - opioid
KW - acetycholine
KW - M3 muscarinic receptor
KW - G-protein
KW - receptor
KW - signaling
KW - lipid
U2 - 10.1016/j.bbamcr.2009.05.002
DO - 10.1016/j.bbamcr.2009.05.002
M3 - Article
SN - 0167-4889
VL - 1793
SP - 1289
EP - 1303
JO - Biochimica et Biophysica Acta. Molecular Cell Research
JF - Biochimica et Biophysica Acta. Molecular Cell Research
IS - 7
ER -