Influence of phenylmethylsulfonyl fluoride on anandamide brain levels and pharmacological effects

Wiley, Jenny L.; Dewey, Michael A.; Jefferson, Renée G.; Winckler, Ramona; Bridgen, D.Troy; Willoughby, Karen A.; Martin, Billy R.

doi:10.1016/s0024-3205(00)00749-9

Cited by 25 publications

(21 citation statements)

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“…There was approximately a 40% inhibition of FFA production with 10 mm phenylmethylsulfonyl fluoride, a potent inhibitor of FAAH activity consistent with the catalytic mechanism of a Ser hydrolase (Wiley et al, 2000). In contrast, there was only 10% inhibition by 10 m arachidonyl trifluoromethyl ketone (ATMK), an analog of anandamide.…”

Section: Identification Of Nae Metabolites and Subcellular Distributimentioning

confidence: 65%

N-Acylethanolamines Are Metabolized by Lipoxygenase and Amidohydrolase in Competing Pathways during Cottonseed Imbibition

et al. 2002

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Saturated and unsaturated N-acylethanolamines (NAEs) occur in desiccated seeds primarily as 16C and 18C species with N-palmitoylethanolamine and N-linoleoylethanolamine (NAE 18:2) being most abundant. Here, we examined the metabolic fate of NAEs in vitro and in vivo in imbibed cotton (Gossypium hirsutum) seeds. When synthetic [1-14 C]Npalmitoylethanolamine was used as a substrate, free fatty acids (FFA) were produced by extracts of imbibed cottonseeds. When synthetic [1-14 C]NAE 18:2 was used as a substrate, FFA and an additional lipid product(s) were formed. On the basis of polarity, we presumed that the unidentified lipid was a product of the lipoxygenase (LOX) pathway and that inclusion of the characteristic LOX inhibitors nordihydroguaiaretic acid and eicosatetraynoic acid reduced its formation in vitro and in vivo. The conversion of NAE 18:2 in imbibed cottonseed extracts to 12-oxo-13-hydroxy-N-(9Z)-octadecanoylethanolamine was confirmed by gas chromatography-mass spectrometry, indicating the presence of 13-LOX and 13-allene oxide synthase, which metabolized NAE 18:2. Cell fractionation studies showed that the NAE amidohydrolase, responsible for FFA production, was associated mostly with microsomes, whereas LOX, responsible for NAE 18:2-oxylipin production, was distributed in cytosol-enriched fractions and microsomes. The highest activity toward NAE by amidohydrolase was observed 4 to 8 h after imbibition and by LOX 8 h after imbibition. Our results collectively indicate that two pathways exist for NAE metabolism during seed imbibition: one to hydrolyze NAEs in a manner similar to the inactivation of endocannabinoid mediators in animal systems and the other to form novel NAE-derived oxylipins. The rapid depletion of NAEs by these pathways continues to point to a role for NAE metabolites in seed germination.In mammalian cells, N-acylethanolamines (NAEs) have varied physiological roles. N-Arachidonylethanolamine (anandamide), a type of NAE in mammalian brain tissue, is an endogenous ligand for the cannabinoid receptor and modulates neurotransmission. Anandamide also can activate vanilloid (capsaicin) receptors and function as an endogenous analgesic (Pertwee, 2001), and appears to be involved in neuroprotection (Hansen et al., 2000;Van der Stelt et al., 2001). In other animal tissues, NAEs have been implicated in immunomodulation (Buckley et al., 2000), synchronization of embryo development (Paria and Dey, 2000), and induction of apoptosis (Sarker et al., 2000). These endogenous bioactive molecules termed "endocannabinoids" are hydrolyzed by fatty acid amidohydrolase (AHase) to terminate their signaling functions.In plants NAEs are present in substantial amounts in desiccated cotton (Gossypium hirsutum) seeds (1.6 g Ϫ1 g fresh weight), and their levels decline after a few hours of imbibition . Individual NAEs were identified predominantly as 16C and 18C species with N-palmitoylethanolamine (NAE 16:0) and N-linoleoylethanolamine (NAE 18:2) being the most abundant. NAEs in both plant and animal cells are deri...

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Section: Identification Of Nae Metabolites and Subcellular Distributimentioning

confidence: 65%

N-Acylethanolamines Are Metabolized by Lipoxygenase and Amidohydrolase in Competing Pathways during Cottonseed Imbibition

et al. 2002

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“…28,29 As shown in Figure 2a, methanadamide also induced cell death in primary neuronal cultures, albeit at somewhat higher concentrations than required for anandamide. Significant decreases of cell viability were observed in meth-anandamide-treated cells at concentrations of 25 and 50 mM in CGC and RCN cultures, respectively.…”

Section: The Metabolically Stable Anandamide Analog Methanandamide Camentioning

confidence: 87%

Anandamide-induced cell death in primary neuronal cultures: role of calpain and caspase pathways

et al. 2004

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Anandamide (arachidonoylethanolamide or AEA) is an endocannabinoid that acts at vanilloid (VR1) as well as at cannabinoid (CB1/CB2) and NMDA receptors. Here, we show that AEA, in a dose-dependent manner, causes cell death in cultured rat cortical neurons and cerebellar granule cells. Inhibition of CB1, CB2, VR1 or NMDA receptors by selective antagonists did not reduce AEA neurotoxicity. Anandamideinduced neuronal cell loss was associated with increased intracellular Ca 2 þ , nuclear condensation and fragmentation, decreases in mitochondrial membrane potential, translocation of cytochrome c, and upregulation of caspase-3-like activity. However, caspase-3, caspase-8 or caspase-9 inhibitors, or blockade of protein synthesis by cycloheximide did not alter anandamide-related cell death. Moreover, AEA caused cell death in caspase-3-deficient MCF-7 cell line and showed similar cytotoxic effects in caspase-9 dominantnegative, caspase-8 dominant-negative or mock-transfected SH-SY5Y neuroblastoma cells. Anandamide upregulated calpain activity in cortical neurons, as revealed by a-spectrin cleavage, which was attenuated by the calpain inhibitor calpastatin. Calpain inhibition significantly limited anandamide-induced neuronal loss and associated cytochrome c release. These data indicate that AEA neurotoxicity appears not to be mediated by CB1, CB2, VR1 or NMDA receptors and suggest that calpain activation, rather than intrinsic or extrinsic caspase pathways, may play a critical role in anandamide-induced cell death.

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“…Indeed, brain levels of both anandamide and arachionic acid are substantial within 5 min or less of i.v. injection with anandamide (Wiley et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Injections of other pharmacological modulators of the arachidonic acid pathway occurred at the following times before injection with anandamide, arachidonic acid, or vehicle: 10 min for indomethacin, aspirin, acetaminophen, esculetin, and phenidone; 15 min for nimesulide and dexamethasone. Choice of pre-test injection times for the cannabinoids (e.g., anandamide, SR141716A, O-1812) and for PMSF was based upon our previous extensive research with these compounds Compton et al, 1996;Di Marzo et al, 2001;Wiley et al, 2000). Pre-injection times for the other compounds were based upon literature reports of previous research with each of these drugs (Flynn et al, 1986;Lucas et al, 2005;Neichi et al, 1983;Pairet and van Ryn, 1998).…”

Section: Methodsmentioning

confidence: 99%

“…Termination of anandamide action may be effected through its rapid metabolism to inactive metabolites (Deutsch and Chin, 1993) and through uptake by a putative anandamide transporter (Beltramo et al, 1997). The rapid metabolic inactivation of anandamide through hydrolysis is mediated by action of fatty acid amide hydrolase (Cravatt et al, 1996;Deutsch and Chin, 1993), with arachidonic acid as the primary metabolite (Wiley et al, 2000;Willoughby et al, 1997). Anandamide may also undergo oxidative metabolism through interaction of its arachidonyl substituent with enzymes in the arachidonic acid cascade ( Fig.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the role of the arachidonic acid cascade in anandamide's in vivo effects in mice

2006

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Influence of phenylmethylsulfonyl fluoride on anandamide brain levels and pharmacological effects

Cited by 25 publications

References 0 publications

N-Acylethanolamines Are Metabolized by Lipoxygenase and Amidohydrolase in Competing Pathways during Cottonseed Imbibition

N-Acylethanolamines Are Metabolized by Lipoxygenase and Amidohydrolase in Competing Pathways during Cottonseed Imbibition

Anandamide-induced cell death in primary neuronal cultures: role of calpain and caspase pathways

Evaluation of the role of the arachidonic acid cascade in anandamide's in vivo effects in mice

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