Functional lipidomics. Calcium-independent activation of endocannabinoid/endovanilloid lipid signalling in sensory neurons by protein kinases C and A and thrombin

Vittorio Vellani; Stefania Petrosino; Luciano De Petrocellis; Marta Valenti; Massimiliano Prandini; Pier Cosimo Magherini; Peter McNaughton; Vincenzo Di Marzo

doi:10.1016/j.neuropharm.2008.01.010

Functional lipidomics. Calcium-independent activation of endocannabinoid/endovanilloid lipid signalling in sensory neurons by protein kinases C and A and thrombin

Vittorio Vellani, Stefania Petrosino, Luciano De Petrocellis, Marta Valenti, Massimiliano Prandini, Pier Cosimo Magherini, Peter McNaughton, Vincenzo Di Marzo^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

44 Citations (Scopus)

Abstract

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 Ca(2+) 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.

Original language	English
Pages (from-to)	1274-1279
Number of pages	6
Journal	Neuropharmacology
Volume	55
Issue number	8
DOIs	https://doi.org/10.1016/j.neuropharm.2008.01.010
Publication status	Published - Dec 2008

Keywords

TRPV1
CB1
Anandamide
2-Arachidonoylglycerol
Cannabinoid
Signalling
Vanilloid
Channel
Metabotropic
RECEPTOR POTENTIAL VANILLOID-1
CAPSAICIN RECEPTOR
CANNABINOID RECEPTOR
VR1 RECEPTORS
ENDOGENOUS CANNABINOIDS
THERMAL HYPERALGESIA
TRPV1 CHANNELS
ANANDAMIDE
PHOSPHORYLATION
RELEASE

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10.1016/j.neuropharm.2008.01.010

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Vellani, V., Petrosino, S., De Petrocellis, L., Valenti, M., Prandini, M., Magherini, P. C., McNaughton, P., & Di Marzo, V. (2008). Functional lipidomics. Calcium-independent activation of endocannabinoid/endovanilloid lipid signalling in sensory neurons by protein kinases C and A and thrombin. Neuropharmacology, 55(8), 1274-1279. https://doi.org/10.1016/j.neuropharm.2008.01.010

@article{2197a81d16ab40839982cf68f2ce6775,

title = "Functional lipidomics. Calcium-independent activation of endocannabinoid/endovanilloid lipid signalling in sensory neurons by protein kinases C and A and thrombin",

abstract = "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 Ca(2+) 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.",

keywords = "TRPV1, CB1, Anandamide, 2-Arachidonoylglycerol, Cannabinoid, Signalling, Vanilloid, Channel, Metabotropic, RECEPTOR POTENTIAL VANILLOID-1, CAPSAICIN RECEPTOR, CANNABINOID RECEPTOR, VR1 RECEPTORS, ENDOGENOUS CANNABINOIDS, THERMAL HYPERALGESIA, TRPV1 CHANNELS, ANANDAMIDE, PHOSPHORYLATION, RELEASE",

author = "Vittorio Vellani and Stefania Petrosino and {De Petrocellis}, Luciano and Marta Valenti and Massimiliano Prandini and Magherini, {Pier Cosimo} and Peter McNaughton and {Di Marzo}, Vincenzo",

year = "2008",

month = dec,

doi = "10.1016/j.neuropharm.2008.01.010",

language = "English",

volume = "55",

pages = "1274--1279",

journal = "Neuropharmacology",

issn = "0028-3908",

publisher = "Elsevier Limited",

number = "8",

}

Vellani, V, Petrosino, S, De Petrocellis, L, Valenti, M, Prandini, M, Magherini, PC, McNaughton, P & Di Marzo, V 2008, 'Functional lipidomics. Calcium-independent activation of endocannabinoid/endovanilloid lipid signalling in sensory neurons by protein kinases C and A and thrombin', Neuropharmacology, vol. 55, no. 8, pp. 1274-1279. https://doi.org/10.1016/j.neuropharm.2008.01.010

TY - JOUR

T1 - Functional lipidomics. Calcium-independent activation of endocannabinoid/endovanilloid lipid signalling in sensory neurons by protein kinases C and A and thrombin

AU - Vellani, Vittorio

AU - Petrosino, Stefania

AU - De Petrocellis, Luciano

AU - Valenti, Marta

AU - Prandini, Massimiliano

AU - Magherini, Pier Cosimo

AU - McNaughton, Peter

AU - Di Marzo, Vincenzo

PY - 2008/12

Y1 - 2008/12

N2 - 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 Ca(2+) 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.

AB - 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 Ca(2+) 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.

KW - TRPV1

KW - CB1

KW - Anandamide

KW - 2-Arachidonoylglycerol

KW - Cannabinoid

KW - Signalling

KW - Vanilloid

KW - Channel

KW - Metabotropic

KW - RECEPTOR POTENTIAL VANILLOID-1

KW - CAPSAICIN RECEPTOR

KW - CANNABINOID RECEPTOR

KW - VR1 RECEPTORS

KW - ENDOGENOUS CANNABINOIDS

KW - THERMAL HYPERALGESIA

KW - TRPV1 CHANNELS

KW - ANANDAMIDE

KW - PHOSPHORYLATION

KW - RELEASE

U2 - 10.1016/j.neuropharm.2008.01.010

DO - 10.1016/j.neuropharm.2008.01.010

M3 - Article

SN - 0028-3908

VL - 55

SP - 1274

EP - 1279

JO - Neuropharmacology

JF - Neuropharmacology

IS - 8

ER -

Functional lipidomics. Calcium-independent activation of endocannabinoid/endovanilloid lipid signalling in sensory neurons by protein kinases C and A and thrombin

Abstract

Keywords

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