Synthesis and biological evaluation of novel amides of polyunsaturated fatty acids with dopamine

Безуглов, В. В.; Bobrov, M. Yu.; Gretskaya, N. M.; Gonchar, Alla; Зинченко, Г. Н.; Melck, Dominique; Bisogno, Tiziana; Marzo, Vincenzo Di; Kuklev, Dmitry V.; Rossi, Jean‐Claude; Vidal, Jean‐Pierre; Durand, Thierry

doi:10.1016/s0960-894x(00)00689-2

Cited by 73 publications

(55 citation statements)

References 15 publications

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“…We have previously shown a functional role of TRPV1 in the ventral midbrain (Marinelli et al, 2003(Marinelli et al, , 2005 and other studies have demonstrated a presynaptic modulation of neurotransmission by CB1 in the same area Melis et al, 2004). Compared with AEA, NADA is more potent at TRPV1 and less potent but more efficacious at CB1-R (Bisogno et al, 2000;Bezuglov et al, 2001;Huang et al, 2002b).…”

Section: Introductionmentioning

confidence: 85%

N-Arachidonoyl-Dopamine Tunes Synaptic Transmission onto Dopaminergic Neurons by Activating both Cannabinoid and Vanilloid Receptors

Marinelli

Marzo

Florenzano

et al. 2006

Neuropsychopharmacol

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149

117

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In the present study, we used electrophysiological, biochemical, and confocal microscopy techniques, to investigate the functional role of transient receptor potential vanilloid type 1 (TRPV1) and cannabinoid type 1 receptors (CB1-R) in the substantia nigra pars compacta (SNpc) and their stimulation by the endocannabinoid N-arachidonoyl-dopamine (NADA). Liquid chromatography-mass spectrometry analyses revealed that a NADA-like compound is produced in substantia nigra slices, in conditions of hyperactivity. Moreover, the functional role of both TRPV1 and CB1-R in modulating synaptic transmission in this area was suggested by confocal microscopy data, showing TRPV1 and CB1-R immunoreactivity in punctate structures, probably representing synaptic contacts on cell bodies of the SNpc. In patch-clamp recordings from dopamine (DA) neurons of the SNpc, we found that NADA increases or reduces glutamatergic transmission onto DA neurons by activating TRPV1 and CB1 receptors, respectively, whereas it decreases GABAergic transmission via CB1 stimulation. Facilitation of glutamate release through TRPV1 was blocked in the presence of a selective blocker of the putative endocannabinoid membrane transporter (EMT), indicating that NADA needs to be taken up by cells to interact with this receptor. In line with these data, biochemical results demonstrated that NADA selectively acted at CB1-R when its re-uptake was blocked. Altogether these data demonstrate a significant role exerted by the endocannabinoid/endovanilloid NADA in the regulation of synaptic transmission to DA neurons of the SNpc. Moreover, they highlight a key function of the EMT transporter in promoting the stimulation of TRPV1 or CB1-R, thus favoring facilitation or inhibition of glutamate synaptic release.

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Section: Introductionmentioning

confidence: 85%

N-Arachidonoyl-Dopamine Tunes Synaptic Transmission onto Dopaminergic Neurons by Activating both Cannabinoid and Vanilloid Receptors

Marinelli

Marzo

Florenzano

et al. 2006

Neuropsychopharmacol

Self Cite

149

117

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“…These studies led us to hypothesize that NADA may moderate sepsis-induced inflammation. The majority of the in vivo work on NADA has focused on its neurologic and behavioral effects, and NADA's effects on inflammation have not been characterized (2,(35)(36)(37)(38). Although there are mixed studies suggesting that TRPV1 activation affects inflammation in models of sepsis, to our knowledge, no prior study has investigated in vivo the role of NADA or the NADA-TRPV1 axis in sepsis (17,27,39,40).…”

Section: T He Endogenous Lipid N-arachidonoyl Dopamine (Nada)mentioning

confidence: 99%

N-Arachidonoyl Dopamine Modulates Acute Systemic Inflammation via Nonhematopoietic TRPV1

Lawton

Tran

et al. 2017

The Journal of Immunology

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N-Arachidonoyl dopamine (NADA) is an endogenous lipid that potently activates the transient receptor potential vanilloid 1 (TRPV1), which mediates pain and thermosensation. NADA is also an agonist of cannabinoid receptors 1 and 2. We have reported that NADA reduces the activation of cultured human endothelial cells by LPS and TNF-α. Thus far, in vivo studies using NADA have focused on its neurologic and behavioral roles. In this article, we show that NADA potently decreases in vivo systemic inflammatory responses and levels of the coagulation intermediary plasminogen activator inhibitor 1 in three mouse models of inflammation: LPS, bacterial lipopeptide, and polymicrobial intra-abdominal sepsis. We also found that the administration of NADA increases survival in endotoxemic mice. Additionally, NADA reduces blood levels of the neuropeptide calcitonin gene-related peptide but increases the neuropeptide substance P in LPS-treated mice. We demonstrate that the anti-inflammatory effects of NADA are mediated by TRPV1 expressed by nonhematopoietic cells and provide data suggesting that neuronal TRPV1 may mediate NADA’s anti-inflammatory effects. These results indicate that NADA has novel TRPV1-dependent anti-inflammatory properties and suggest that the endovanilloid system might be targeted therapeutically in acute inflammation.

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“…Amidas graxas biologicamente ativas, palmitoiletanolamida (1), anandamida (2), cis-oleamida (3), oleiletanolamida (4) e N-benzil-Ztetracosenamida (5) Os ácidos graxos 6a-c (Esquema 1) foram esterificados utilizando-se H 2 SO 4 e metanol a temperatura de 65 o C por 4 h, formando os respectivos ésteres metílicos graxos 7a-c.…”

Section: 46unclassified

“…[1][2][3][4][5][6] Esta classe de compostos tem sido naturalmente encontrada em vegetais terrestres e aquáticos, em animais e micro-organismos. No reino vegetal, estão presentes nas algas Rizoclonium hierogliphicun, Zoostera marina e Sebastes mentella, nos vegetais Lepidium meyenii (maca) e Zanthoxylum sp.…”

Section: Introductionunclassified

“…O princípio ativo responsável por essas ações foi atribuído à palmitoiletanolamida (1) a primeira amida graxa isolada (Figura 1). 31 A identificação das amidas graxas, a N-araquidonoiletanolamida, também chamada de anandamida (AEA, 2) 32 e a cis-oleamida (cOA, 3), 33 membros mais conhecidos e estudados desta grande família, abriu caminhos para a investigação das propriedades farmacológicas, identificação, síntese e isolamento de novas amidas graxas como, por exemplo, oleiletanolamida (4) e N-benzil-15-Z-tetracosenamida (5, macamida) (Figura 1). 10,34 O objetivo deste trabalho foi sintetizar novas amidas graxas derivadas de diferentes aminas a partir da reação de aminólise de ésteres graxos saturados e insaturados.…”

Section: Introductionunclassified

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Síntese de novas amidas graxas a partir da aminólise de ésteres metílicos

et al. 2010

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. Itália km 08 s/n, 96203-000 Rio Grande -RS, Brasil Recebido em 11/11/09; aceito em 17/2/10; publicado na web em 21/5/10 SYNTHESIS OF NEW FATTY ACIDS AMIDES FROM AMINOLYSIS OF FAMES. Recent biochemical and pharmacological studies have led to the characterization of different fatty acid amides as a new family of biologically active lipids. Here, we describe the synthesis of new amides from C16:0, 18:0, 18:1 and 18:1, OH fatty acids (FFA) families with cyclic and acyclic amines and demonstrate for the first time that these compounds produce citotoxic effects. Application of this method to the synthesis of fatty acid amides was performed using the esters aminolysis as a key step and various carboxylic amides were prepared in good yield from fatty acid methyl esters (FAMEs).

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Synthesis and biological evaluation of novel amides of polyunsaturated fatty acids with dopamine

Cited by 73 publications

References 15 publications

N-Arachidonoyl-Dopamine Tunes Synaptic Transmission onto Dopaminergic Neurons by Activating both Cannabinoid and Vanilloid Receptors

N-Arachidonoyl-Dopamine Tunes Synaptic Transmission onto Dopaminergic Neurons by Activating both Cannabinoid and Vanilloid Receptors

N-Arachidonoyl Dopamine Modulates Acute Systemic Inflammation via Nonhematopoietic TRPV1

Síntese de novas amidas graxas a partir da aminólise de ésteres metílicos

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