N-arachidonoylethanolamine (anandamide, AEA), is a full agonist at both cannabinoid CB, receptors and "transient receptor potential vanilloid" type I (TRPV1) channels, and N-palmitoylethanolamine (PEA) potentiates these effects. In neurons of the rat dorsal root ganglia (DRG), TRPV1 is activated and/or sensitised by AEA as well as upon activation of protein kinases C (PKC) and A (PKA). We investigated here the effect on AEA levels of PKC and PKA activators in DRG neurons. AEA levels were significantly enhanced by both phorbol-miristoyl-acetate (PMA), a typical PKC activator, and forskolin (FSK), an adenylate cyclase stimulant, as well as by thrombin, which also activates PKC by stimulating protease-activated receptors (PARs). The levels of the other endocannabinoid and TRPV1-inactive compound, 2-arachidonoylglycerol (2-AG), were enhanced only by thrombin and to a lesser extent than AEA, whereas PEA was not affected by any of the treatments. Importantly, FSK- and PMA-induced elevation of AEA levels was not sensitive to intracellular Ca2+ chelation with BAPTA-acetoxymethyl (AM) ester. In human embryonic kidney (HEK-293) cells, which constitutively express PARs, thrombin, PMA and FSK elevated AEA levels, and the effects of the two former compounds were counteracted by the PKC inhibitor, RO318220, whereas the effect of FSK was reduced by the PKA inhibitor RpcAMPs. In conclusion, we report that AEA levels are stimulated by both PKC, either directly or after thrombin receptor activation, and PKA, possibly in a way independent from intracellular calcium. Since AEA activates TRPV1, these findings may suggest the existence of an amplificatory cascades on this receptor in sensory neurons. (C) 2008 Elsevier Ltd. All rights reserved.
Attenzione! Scheda prodotto non ancora validata dall'Ateneo
Dati e metadati della pubblicazione sono in fase di verifica da parte dell'Ateneo. In caso di errori o violazione dei diritti d'autore, contattare: firstname.lastname@example.org
|Anno di pubblicazione:||2008|
|Titolo:||Functional lipidomics. Calcium-independent activation of endocannabinoid/endovanilloid lipid signalling in sensory neurons by protein kinases C and A and thrombin|
|Autori:||V. Vellani; S. Petrosino; L. De Petrocellis; M. Valenti; M. Prandini; P.C. Magherini; P.A. McNaughton; V. Di Marzo|
|Digital Object Identifier (DOI):||10.1016/j.neuropharm.2008.01.010|
|Appare nelle tipologie:||Articolo su rivista|
File in questo prodotto:
|M1.pdf||Post-print||NON PUBBLICO - Accesso privato/ristretto||Administrator|
I documenti presenti in Iris Unimore sono rilasciati con licenza Creative Commons Attribuzione - Non commerciale - Non opere derivate 3.0 Italia, salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris