title: Mechanisms for the coupling of cannabinoid receptors to intracellular calcium mobilization in rat insulinoma beta-cells.
abstract: In RIN m5F rat insulinoma beta-cells, agonists at cannabinoid CB(1) receptors modulate insulin release. Here we investigated in these cells the effect of the activation of cannabinoid CB(1) and CB(2) receptors on intracellular Ca(2+) ([Ca(2+)](i)). The CB(1) agonist arachidonoyl-chloro-ethanolamide (ACEA), and the CB(2) agonist JWH133, elevated [Ca(2+)](i) in a way sensitive to the inhibitor of phosphoinositide-specific phospholipase C (PI-PLC), U73122 (but not to pertussis toxin and forskolin), and independently from extracellular Ca(2+). PI-PLC-dependent Ca(2+) mobilization by ACEA was entirely accounted for by activation of inositol-1,3,4-phosphate (IP(3)) receptors on the endoplasmic reticulum (ER), whereas the effect of JWH133 was not sensitive to all tested inhibitors of IP(3) and ryanodine receptors. ACEA, but not JWH133, significantly inhibited the effect on [Ca(2+)](i) of bombesin, which acts via G(q/11)- and PI-PLC-coupled receptors in insulinoma cells. The endogenous CB(1) agonists, anandamide and N-arachidonoyldopamine, which also activate transient receptor potential vanilloid type 1 (TRPV1) receptors expressed in RIN m5F cells, elevated [Ca(2+)](i) in the presence of extracellular Ca(2+) in a way sensitive to both CB(1) and TRPV1 antagonists. These results suggest that, in RIN m5F cells, CB(1) receptors are coupled to PI-PLC-mediated mobilization of [Ca(2+)](i) and might inhibit bombesin signaling.
authors.affiliation: Endocannabinoid Research Group, Institute of Cybernetics, National Research Council, Via Campi Flegrei 34, Comprensorio Olivetti, 80078 Pozzuoli, Naples, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: De Petrocellis
authors.forename: Pietro
authors.initials: P
authors.lastname: Marini
authors.forename: Isabel
authors.initials: I
authors.lastname: Matias
authors.forename: Aniello Schiano
authors.initials: AS
authors.lastname: Moriello
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Starowicz
authors.forename: Luigia
authors.initials: L
authors.lastname: Cristino
authors.forename: Santosh
authors.initials: S
authors.lastname: Nigam
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001839:Bombesin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002186:Cannabinoids / Q000378:metabolism; D002211:Capsaicin / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D005576:Colforsin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D004963:Estrenes / Q000378:metabolism; D007340:Insulinoma / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D037342:Pertussis Toxin / Q000378:metabolism; D054801:Phosphoinositide Phospholipase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011760:Pyrrolidinones / Q000378:metabolism; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018689:Sensory System Agents / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019284:Thapsigargin / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D002186:Cannabinoids; D004791:Enzyme Inhibitors; D004963:Estrenes; D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents; D011760:Pyrrolidinones; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D018689:Sensory System Agents; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C119325:arachidonyl-2-chloroethylamide; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D005576:Colforsin; D019284:Thapsigargin; D013759:Dronabinol; D037342:Pertussis Toxin; D054801:Phosphoinositide Phospholipase C; D001839:Bombesin; C062018:HU 211; D002211:Capsaicin; D002118:Calcium; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC