Multiple pathways involved in the biosynthesis of anandamide

Liu, Jie; Wang, Lei; Harvey−White, Judith; Huang, Boji; Kim, Hee‐Yong; Luquet, Serge; Palmiter, Richard D.; Krystal, Gerald; Rai, Ravi; Mahadevan, Anu; Razdan, Raj K.; Kunos, George

doi:10.1016/j.neuropharm.2007.05.020

Cited by 269 publications

(217 citation statements)

References 27 publications

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“…Unfortunately, several limitations hinder the ability to probe for group-related differences in AEA biosynthesis. For example, the pathway(s) for AEA synthesis have not been unequivocally identified (Leung et al, 2006;Simon and Cravatt, 2008;Liu et al, 2008), and there are presently no selective inhibitors available for any of the enzymes implicated in AEA biosynthesis. The volitional nature of nicotine exposure may also influence the neurochemical stimuli that provoke AEA production.…”

Section: Endocannabinoid Levels Following Nicotine Exposure Mw Buczynmentioning

confidence: 99%

The Volitional Nature of Nicotine Exposure Alters Anandamide and Oleoylethanolamide Levels in the Ventral Tegmental Area

Buczynski

Polis

Parsons

2012

Neuropsychopharmacol

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Cannabinoid-1 receptors (CB 1 ) have an important role in nicotine reward and their function is disrupted by chronic nicotine exposure, suggesting nicotine-induced alterations in endocannabinoid (eCB) signaling. However, the effects of nicotine on brain eCB levels have not been rigorously evaluated. Volitional intake of nicotine produces physiological and behavioral effects distinct from forced drug administration, although the mechanisms underlying these effects are not known. This study compared the effects of volitional nicotine self-administration (SA) and forced nicotine exposure (yoked administration (YA)) on levels of eCBs and related neuroactive lipids in the ventral tegmental area (VTA) and other brain regions. Brain lipid levels were indexed both by in vivo microdialysis in the VTA and lipid extractions from brain tissues. Nicotine SA, but not YA, reduced baseline VTA dialysate oleoylethanolamide (OEA) levels relative to nicotine-naïve controls, and increased anandamide (AEA) release during nicotine intake. In contrast, all nicotine exposure paradigms increased VTA dialysate 2-arachidonoyl glycerol (2-AG) levels. Thus, nicotine differentially modulates brain lipid (2-AG, AEA, and OEA) signaling, and these modulations are influenced by the volitional nature of the drug exposure. Corresponding bulk tissue analysis failed to identify these lipid changes. Nicotine exposure had no effect on fatty acid amide hydrolase activity in the VTA, suggesting that changes in AEA and OEA signaling result from alterations in their nicotine-induced biosynthesis. Both CB 1 (by AEA and 2-AG) and non-CB 1 (by OEA) targets can alter the excitability and activity of the dopaminergic neurons in the VTA. Collectively, these findings implicate disrupted lipid signaling in the motivational effects of nicotine.

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Section: Endocannabinoid Levels Following Nicotine Exposure Mw Buczynmentioning

confidence: 99%

The Volitional Nature of Nicotine Exposure Alters Anandamide and Oleoylethanolamide Levels in the Ventral Tegmental Area

Buczynski

Polis

Parsons

2012

Neuropsychopharmacol

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“…Other enzymatic pathways have also been implicated in the biosynthesis of anandamide [30][31][32][33][34][35] but, as yet, definite proof that these are involved in in vivo production of anandamide in the brain has not been forthcoming. It is possible that multiple and potentially interacting pathways are involved, which may make it difficult to pinpoint roles for particular enzymes.…”

Section: Introduction To Endocannabinoid Signallingmentioning

confidence: 99%

The evolution and comparative neurobiology of endocannabinoid signalling

Elphick

2012

Phil. Trans. R. Soc. B

153

137

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CB 1 -and CB 2 -type cannabinoid receptors mediate effects of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide in mammals. In canonical endocannabinoid-mediated synaptic plasticity, 2-AG is generated postsynaptically by diacylglycerol lipase alpha and acts via presynaptic CB 1 -type cannabinoid receptors to inhibit neurotransmitter release. Electrophysiological studies on lampreys indicate that this retrograde signalling mechanism occurs throughout the vertebrates, whereas system-level studies point to conserved roles for endocannabinoid signalling in neural mechanisms of learning and control of locomotor activity and feeding. CB 1 /CB 2 -type receptors originated in a common ancestor of extant chordates, and in the sea squirt Ciona intestinalis a CB 1 / CB 2 -type receptor is targeted to axons, indicative of an ancient role for cannabinoid receptors as axonal regulators of neuronal signalling. Although CB 1 /CB 2 -type receptors are unique to chordates, enzymes involved in biosynthesis/inactivation of endocannabinoids occur throughout the animal kingdom. Accordingly, non-CB 1 /CB 2 -mediated mechanisms of endocannabinoid signalling have been postulated. For example, there is evidence that 2-AG mediates retrograde signalling at synapses in the nervous system of the leech Hirudo medicinalis by activating presynaptic transient receptor potential vanilloid-type ion channels. Thus, postsynaptic synthesis of 2-AG or anandamide may be a phylogenetically widespread phenomenon, and a variety of proteins may have evolved as presynaptic (or postsynaptic) receptors for endocannabinoids.

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“…1), are phospholipid-derived lipids containing an arachidonic acid chain in their chemical structure. Anabolic and catabolic enzymes for ECs are still being identified and cloned [4][5][6]. These proteins, together with the ECs and the type 1 and 2 cannabinoid receptors (CB 1 and CB 2 ), constitute the EC system.…”

Section: Introductionmentioning

confidence: 99%

The endocannabinoid system in obesity and type 2 diabetes

2008

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Endocannabinoids (ECs) are defined as endogenous agonists of cannabinoid receptors type 1 and 2 (CB 1 and CB 2 ). ECs, EC anabolic and catabolic enzymes and cannabinoid receptors constitute the EC signalling system. This system participates in the control of lipid and glucose metabolism at several levels, with the possible endpoint of the accumulation of energy as fat. Following unbalanced energy intake, however, the EC system becomes dysregulated, and in most cases overactive, in several organs participating in energy homeostasis, particularly, in intraabdominal adipose tissue. This dysregulation might contribute to excessive visceral fat accumulation and reduced adiponectin release from this tissue, and to the onset of several cardiometabolic risk factors that are associated with obesity and type 2 diabetes. This phenomenon might form the basis of the mechanism of action of CB 1 antagonists/ inverse agonists, recently developed by several pharmaceutical companies as adjuvants to lifestyle modification for weight reduction, glycaemic control and dyslipidaemia in obese and type 2 diabetes patients. It also helps to explain why some of the beneficial actions of these new therapeutics appear to be partly independent from weight loss.

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Multiple pathways involved in the biosynthesis of anandamide

Cited by 269 publications

References 27 publications

The Volitional Nature of Nicotine Exposure Alters Anandamide and Oleoylethanolamide Levels in the Ventral Tegmental Area

The Volitional Nature of Nicotine Exposure Alters Anandamide and Oleoylethanolamide Levels in the Ventral Tegmental Area

The evolution and comparative neurobiology of endocannabinoid signalling

The endocannabinoid system in obesity and type 2 diabetes

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