Background: The endocannabinoid 2-arachidonoylglycerol (2-AG) is an endogenous lipid that acts through the activation of G-protein-coupled cannabinoid receptors and plays essential roles in many physiological contexts. In the cardiovascular system 2-AG is generated by both activated endothelial cells and platelets, and participates in the regulation of inflammation and thrombosis. Although human platelets actively metabolize endocannabinoids, 2-AG also binds to platelet surface and leads to cell activation. Objective: To investigate the biological consequence of 2-AG interactions with human platelets and to clarify the role of cannabinoid receptors. Methods: Gel-filtered platelets were stimulated with 2-AG in the presence or absence of various inhibitors. Platelet aggregation and secretion were measured in a lumiaggregometer. Calcium ion movements were measured in FURA-2 loaded platelets. Thromboxane A(2) (TxA(2)) generation was evaluated as Thromboxane B-2 accumulation with a commercial EIA assay. Results: 2-AG induced platelet shape change, aggregation and secretion with a dose-dependent mechanism that required engagement of platelet TxA(2) receptors. 2-AG caused also cytosolic calcium increase; however, it was totally dependent on availability of TxA(2). Indeed 2-AG was able to induce a robust generation of TxA(2) through the cyclooxygenase pathway. Treatment of platelets with inhibitors of monoacylglycerol lipase and fatty acid amide hydrolase did not affect the activation induced by 2-AG. Moreover, neither CB1 and CB2 proteins nor CB1/CB2 mRNAs were detected in platelets. Conclusions: 2-AG can be considered a new physiologic platelet agonist able to induce full platelet activation and aggregation with a non-CB1/CB2 receptor-mediated mechanism.

Baldassarri, S., Bertoni, A., Bagarotti, A., Sarasso, C., Zanfa, M., Catani, M.v., et al. (2008). The endocannabinoid 2-arachidonoylglycerol activates human platelets through non-CB1/CB2 receptors, 6(10), 1772-1779 [10.1111/j.1538-7836.2008.03093.x].

The endocannabinoid 2-arachidonoylglycerol activates human platelets through non-CB1/CB2 receptors

CATANI, MARIA VALERIA;AVIGLIANO, LUCIANA;
2008-01-01

Abstract

Background: The endocannabinoid 2-arachidonoylglycerol (2-AG) is an endogenous lipid that acts through the activation of G-protein-coupled cannabinoid receptors and plays essential roles in many physiological contexts. In the cardiovascular system 2-AG is generated by both activated endothelial cells and platelets, and participates in the regulation of inflammation and thrombosis. Although human platelets actively metabolize endocannabinoids, 2-AG also binds to platelet surface and leads to cell activation. Objective: To investigate the biological consequence of 2-AG interactions with human platelets and to clarify the role of cannabinoid receptors. Methods: Gel-filtered platelets were stimulated with 2-AG in the presence or absence of various inhibitors. Platelet aggregation and secretion were measured in a lumiaggregometer. Calcium ion movements were measured in FURA-2 loaded platelets. Thromboxane A(2) (TxA(2)) generation was evaluated as Thromboxane B-2 accumulation with a commercial EIA assay. Results: 2-AG induced platelet shape change, aggregation and secretion with a dose-dependent mechanism that required engagement of platelet TxA(2) receptors. 2-AG caused also cytosolic calcium increase; however, it was totally dependent on availability of TxA(2). Indeed 2-AG was able to induce a robust generation of TxA(2) through the cyclooxygenase pathway. Treatment of platelets with inhibitors of monoacylglycerol lipase and fatty acid amide hydrolase did not affect the activation induced by 2-AG. Moreover, neither CB1 and CB2 proteins nor CB1/CB2 mRNAs were detected in platelets. Conclusions: 2-AG can be considered a new physiologic platelet agonist able to induce full platelet activation and aggregation with a non-CB1/CB2 receptor-mediated mechanism.
2008
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/10 - BIOCHIMICA
English
2-Arachidonoylglycerol; Cannabinoid receptors; Platelets; Thromboxane A2
Baldassarri, S., Bertoni, A., Bagarotti, A., Sarasso, C., Zanfa, M., Catani, M.v., et al. (2008). The endocannabinoid 2-arachidonoylglycerol activates human platelets through non-CB1/CB2 receptors, 6(10), 1772-1779 [10.1111/j.1538-7836.2008.03093.x].
Baldassarri, S; Bertoni, A; Bagarotti, A; Sarasso, C; Zanfa, M; Catani, Mv; Avigliano, L; Maccarrone, M; Torti, M; Sinigaglia, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/27043
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