Mechanisms for the coupling of cannabinoid receptors to intracellular calcium mobilization in rat insulinoma beta-cells

Luciano De Petrocellis, Pietro Marini, Isabel Matias, Aniello Schiano Moriello, Katarzyna Starowicz, Luigia Cristino, Santosh Nigam, Vincenzo Di Marzo

Research output: Contribution to journalArticle

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Abstract

In RIN m5F rat insulinoma ß-cells, agonists at cannabinoid CB1 receptors modulate insulin release. Here we investigated in these cells the effect of the activation of cannabinoid CB1 and CB2 receptors on intracellular Ca2+ ([Ca2+]i). The CB1 agonist arachidonoyl-chloro-ethanolamide (ACEA), and the CB2 agonist JWH133, elevated [Ca2+]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 Ca2+. PI-PLC-dependent Ca2+ mobilization by ACEA was entirely accounted for by activation of inositol-1,3,4-phosphate (IP3) receptors on the endoplasmic reticulum (ER), whereas the effect of JWH133 was not sensitive to all tested inhibitors of IP3 and ryanodine receptors. ACEA, but not JWH133, significantly inhibited the effect on [Ca2+]i of bombesin, which acts via Gq/11- and PI-PLC-coupled receptors in insulinoma cells. The endogenous CB1 agonists, anandamide and N-arachidonoyldopamine, which also activate transient receptor potential vanilloid type 1 (TRPV1) receptors expressed in RIN m5F cells, elevated [Ca2+]i in the presence of extracellular Ca2+ in a way sensitive to both CB1 and TRPV1 antagonists. These results suggest that, in RIN m5F cells, CB1 receptors are coupled to PI-PLC-mediated mobilization of [Ca2+]i and might inhibit bombesin signaling.
Original languageEnglish
Pages (from-to)2993-3004
Number of pages11
JournalExperimental Cell Research
Volume313
Issue number14
DOIs
Publication statusPublished - 15 Aug 2007

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Cannabinoid Receptors
Insulinoma
Phosphoinositide Phospholipase C
Cannabinoid Receptor CB1
Calcium
Inositol 1,4,5-Trisphosphate Receptors
Bombesin
Cannabinoid Receptor CB2
Ryanodine Receptor Calcium Release Channel
Pertussis Toxin
Colforsin
Inositol
Endoplasmic Reticulum
Phosphates
Insulin
anandamide

Keywords

  • anandamide
  • TRPV1
  • cannabinoid receptor
  • bombesin
  • calcium
  • insulinoma ß-cells

Cite this

Mechanisms for the coupling of cannabinoid receptors to intracellular calcium mobilization in rat insulinoma beta-cells. / De Petrocellis, Luciano; Marini, Pietro; Matias, Isabel ; Moriello, Aniello Schiano; Starowicz, Katarzyna; Cristino, Luigia; Nigam, Santosh; Di Marzo, Vincenzo.

In: Experimental Cell Research, Vol. 313, No. 14, 15.08.2007, p. 2993-3004.

Research output: Contribution to journalArticle

De Petrocellis, L, Marini, P, Matias, I, Moriello, AS, Starowicz, K, Cristino, L, Nigam, S & Di Marzo, V 2007, 'Mechanisms for the coupling of cannabinoid receptors to intracellular calcium mobilization in rat insulinoma beta-cells', Experimental Cell Research, vol. 313, no. 14, pp. 2993-3004. https://doi.org/10.1016/j.yexcr.2007.05.012
De Petrocellis, Luciano ; Marini, Pietro ; Matias, Isabel ; Moriello, Aniello Schiano ; Starowicz, Katarzyna ; Cristino, Luigia ; Nigam, Santosh ; Di Marzo, Vincenzo. / Mechanisms for the coupling of cannabinoid receptors to intracellular calcium mobilization in rat insulinoma beta-cells. In: Experimental Cell Research. 2007 ; Vol. 313, No. 14. pp. 2993-3004.
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AU - Marini, Pietro

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AU - Moriello, Aniello Schiano

AU - Starowicz, Katarzyna

AU - Cristino, Luigia

AU - Nigam, Santosh

AU - Di Marzo, Vincenzo

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AB - In RIN m5F rat insulinoma ß-cells, agonists at cannabinoid CB1 receptors modulate insulin release. Here we investigated in these cells the effect of the activation of cannabinoid CB1 and CB2 receptors on intracellular Ca2+ ([Ca2+]i). The CB1 agonist arachidonoyl-chloro-ethanolamide (ACEA), and the CB2 agonist JWH133, elevated [Ca2+]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 Ca2+. PI-PLC-dependent Ca2+ mobilization by ACEA was entirely accounted for by activation of inositol-1,3,4-phosphate (IP3) receptors on the endoplasmic reticulum (ER), whereas the effect of JWH133 was not sensitive to all tested inhibitors of IP3 and ryanodine receptors. ACEA, but not JWH133, significantly inhibited the effect on [Ca2+]i of bombesin, which acts via Gq/11- and PI-PLC-coupled receptors in insulinoma cells. The endogenous CB1 agonists, anandamide and N-arachidonoyldopamine, which also activate transient receptor potential vanilloid type 1 (TRPV1) receptors expressed in RIN m5F cells, elevated [Ca2+]i in the presence of extracellular Ca2+ in a way sensitive to both CB1 and TRPV1 antagonists. These results suggest that, in RIN m5F cells, CB1 receptors are coupled to PI-PLC-mediated mobilization of [Ca2+]i and might inhibit bombesin signaling.

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KW - calcium

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