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Leptin-regulated endocannabinoids are involved in maintaining food intake

It is shown that following temporary food restriction, CB1 receptor knockout mice eat less than their wild-type littermates, and the CB1 antagonist SR141716A reduces food intake in wild- type but not knockout mice, which indicates that endocannabinoids in the hypothalamus may tonically activate CB1 receptors to maintain food intake and form part of the neural circuitry regulated by leptin.
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2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain.

2-Arachidonoylglycerol was shown to bind appreciably to the cannabinoid receptor in competitive inhibition experiments and may be an endogenous cannabinoid receptor ligand in the brain.
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Identification of GPR55 as a lysophosphatidylinositol receptor.

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Biochemistry, pharmacology and physiology of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand.

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Biosynthesis and degradation of anandamide and 2-arachidonoylglycerol and their possible physiological significance.

Evidence is gradually accumulating and indicates that 2-AG is the most efficacious endogenous natural ligand for the cannabinoid receptors, which is a degradation product of arachidonic acid-containing glycerophospholipid such as inositol phospholipids.
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Synaptically Driven Endocannabinoid Release Requires Ca2+-Assisted Metabotropic Glutamate Receptor Subtype 1 to Phospholipase C β4 Signaling Cascade in the Cerebellum

The results strongly suggest that under physiological conditions, excitatory synaptic inputs to PCs activate the Ca2+-assisted mGluR1-PLCβ4 cascade, and thereby produce 2-AG, which retrogradely modulates synaptic transmission to PCs.
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Evidence That 2-Arachidonoylglycerol but Not N-Palmitoylethanolamine or Anandamide Is the Physiological Ligand for the Cannabinoid CB2 Receptor

2-arachidonoylglycerol is the most potent compound among a number of naturally occurring cannabimimetic molecules, and anandamide and N-palmitoylethanolamine, other putative endogenous ligands, were found to be a weak partial agonist and an inactive ligand, respectively.
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Evidence That the Cannabinoid CB1 Receptor Is a 2-Arachidonoylglycerol Receptor

The results strongly suggested that the cannabinoid CB1 receptor is originally a 2-arachidonoylglycerol receptor, and 2-Arachidonoyslglycersol is the intrinsic physiological ligand for the cannabinoidCB1 receptor.
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2-Arachidonoyl-sn-glycero-3-phosphoinositol: a possible natural ligand for GPR55.

This study examined whether LPI is present in rat brain and compared the biological activities of various molecular species of LPI and related molecules using HEK293 cells expressing GPR55, finding that the level of biological activity of the 2-arachidonoyl species is markedly higher than those of others.
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Transacylase-mediated and phosphodiesterase-mediated synthesis of N-arachidonoylethanolamine, an endogenous cannabinoid-receptor ligand, in rat brain microsomes. Comparison with synthesis from free…

Several lines of evidence strongly suggest that the second pathway, rather than the first one, meets the requirements and conditions for the synthesis of various species of N-acylethanolamine including anandamide in the brain.
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