2-arachidonoylglycerol (n.) - 2-arachidonoylglycerol (2-AG) is one of the first-discovered and best-studied endocannabinoids. 2-AG is a ligand for cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2). Generally, 2-AG is produced from the hydrolysis of 2-arachidonate–containing diacylglycerols.
Adenylyl cyclase (n.) - (Adenylate cyclase) Membrane-bound enzyme that catalyzes the formation of cyclic adenosine monophosphate (AMP) from adenosine triphosphate (ATP).
Adiponectin (n.) - Adiponectin is an adipocyte-derived hormone that has antidiabetic, anti-inflammatory, and anti-atherogenic properties. Decreased levels of plasma adiponectin are correlated with insulin resistance, dyslipidemia, and cardiovascular disease. Adiponectin messenger ribonucleic acid and serum levels are decreased in obesity.
Agonist (n.) - A hormone, neurotransmitter, or a drug that binds to a specific site on a “receptor” protein and stimulates a response.
Allele (n.) - One of a set of alternative forms of a gene. In a diploid cell, each gene has two alleles.
AMT (abbr.) (n.) - Anandamide membrane transporter. A putative, facilitated transport mechanism. Following cannabinoid receptor type 1 activation, anandamide, and 2-arachidonoylglycerol (2-AG) are taken up by the AMT. Although data from several biochemical studies support the existence of an AMT, an AMT protein remains to be identified.
Anandamide (n.) - Anandamide (N-arachidonoyl-ethanolamine) is one of the first-discovered and best-studied endocannabinoids. Anandamide is a ligand for cannabinoid receptor type 1 (CB1 ) and cannabinoid receptor type 2 (CB2 ); however, it is functionally more selective for the CB1 receptor.
Anorexigenic (adj.) - Promoting or causing anorexia. An agent that diminishes or controls the appetite.
Antagonist (n.) - A molecule that binds to a receptor but does not induce the necessary conformational change in the receptor to stimulate a cellular response.
Anticipatory nausea (n.) - A previously neutral stimulus (eg, smells of the chemotherapy environment) elicits a conditioned response (eg, anticipatory nausea) after a number of prior pairings. These previously neutral stimuli may then elicit anticipatory nausea in future chemotherapy cycles. Many patients report anticipatory nausea and vomiting upon re-exposure to the cues previously associated with treatment.
Autocrine signaling (n.) - Cell signaling in which a cell secretes signaling molecules that act on itself or on other adjacent cells of the same type. Endocannabinoids act on cells in a paracrine or autocrine manner in peripheral tissues.
Blood-brain barrier (n.) - A physiological mechanism that alters the permeability of brain capillaries so that some substances, such as certain drugs, are prevented from entering brain tissues, while other substances are allowed to enter freely.
BMI (abbr.) (n.) - Body mass index. The BMI is used to express the degree of overweight. Calculated as the body weight in kilograms divided by the square of the height in meters [wt/(ht)2]. A BMI > 30 kg/m2 is synonymous with obesity, except in body builders and other athletes.
Ca2+ (abbr.) (n.) - Calcium is the most abundant mineral in the body. It plays a role in many enzymatic processes and cellular signaling pathways. Stimulation of CB1 and CB2 receptor–coupled signaling pathways can lead to an increased intracellular calcium concentration ([Ca2+]i). The synthesis of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) is stimulated by Ca2+ influx and cell-membrane depolarization.
Cannabidiol (n.) - Cannabidiol is a Cannabis sativa constituent that is devoid of the typical effects of the plant. Cannabidiol antagonizes some undesirable effects of tetrahydrocannabinol, including intoxication, sedation, and tachycardia, while contributing analgesic, anti-emetic, and anticarcinogenic properties. Cannabidiol is being studied as an alternative treatment for schizophrenia.
Cannabinoid (n.) - A cannabinoid is a compound that acts on the cannabinoid receptors. It includes the natural lipophilic products from the flower of Cannabis sativa as well as synthetic drugs.
Cannabis sativa (n.) - The cannabis plant (Cannabis sativa). This herb is also known as hemp or marijuana. Herbal cannabinoids occur uniquely in the cannabis plant. Tetrahydrocannabinol is the major pharmacologically active constituent.
Cardiovascular risk factor (n.) - Any risk factor that is associated with or to which cardiovascular disease (CVD) can be attributed. Examples include obesity, type 2 diabetes, and hypertension. Risk factors may also be behavioral (eg, tobacco smoking) or genetic (eg, family history of CVD).
CB1 receptor (n.) - The cannabinoid receptor type 1 (CB1 receptor) was the first cannabinoid receptor to be characterized. The CB1 receptor is a member of the G protein–coupled receptor superfamily of cell-surface receptors. CB1 receptors are present in many central and peripheral sites involved in the control of energy homeostasis and metabolism, including the brain, adipose tissue, liver, pancreas, gastrointestinal tract, and skeletal muscle.
CB2 receptor (n.) - The cannabinoid receptor type 2 (CB2 receptor) was the second cannabinoid receptor to be characterized. The CB2 receptor is a member of the G protein–coupled receptor superfamily of cell-surface receptors. CB2 receptors are primarily expressed in the immune system but may also be expressed in the brain, pancreas and other peripheral tissues.
CCK (abbr.) (n.) - Cholecystokinin. A hormone released by the gastrointestinal tract that produces satiety signals. CCK is secreted during a meal, and interacts with specific CCK receptors located on the afferent terminals of the vagus nerve. CCK-induced satiety is associated with reduced endocannabinoid system (ECS) activity.
Congeners (n(pl).) - Congeners are related chemicals, eg, derivatives or elements in the same group of the periodic table. Congeners can be compounds closely related to another in composition and exert similar or antagonistic effects. For example, N-palmitoylethanolamine (PEA) is an anandamide congener that is inactive at cannabinoid receptors.
cyclic AMP (cAMP) (n.) - Cyclic adenosine monophosphate. Nucleotide generated from ATP by adenylyl cyclase in response to stimulation of many types of cell-surface receptors. cAMP activates cyclic-AMP-dependent kinase (protein kinase A, PKA).
DAGL (abbr.) (n.) - DAGL (sn-1-selective-diacylglycerol lipase) is the enzyme responsible for the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG).
Dyslipidemia (n.) - An abnormal concentration of lipids or lipoproteins in the blood.
Emesis (n.) - The act or process of vomiting.
EMT (abbr.) (n.) - Endocannabinoid membrane transporters (EMTs) are proteins involved in the membrane transport of endocannabinoids. EMTs may regulate endocannabinoid transport across the blood-brain barrier and through other endothelial cells.
Endocannabinoid system (n.) (N-doe-can-nab-in-oid sǐs'təm) - A complex physiological system that affects multiple metabolic pathways. It is comprised of CB receptors, their endogenous ligands (the endocannabinoids), and the proteins involved in endocannabinoid synthesis and inactivation, as well as the intracellular signaling pathways affected by endocannabinoids. Physiologically, the ECS plays a role in modulating energy balance, feeding behavior, hepatic lipogenesis, and glucose homeostasis. The ECS also participates in numerous other physiologic processes including those related to immune response, neuroprotection, memory and learning, nociception (pain sense), fertility, and bone turnover.
Endocannabinoids (n(pl).) - Endocannabinoids are endogenous cannabinoids. That is, they are agonists for endocannabinoid receptors. Endocannabinoids are derived from long-chain polyunsaturated fatty acids. The family of endogenous agonists for CB1 receptors is larger than initially thought. The first-discovered and best-studied endocannabinoids are anandamide (N-arachidonoyl-ethanolamine) and 2-arachidonoylglycerol (2-AG). Newly proposed endocannabinoids are 2-arachidonyl-glyceryl ether (noladin, 2-AGE), O-arachidonoyl-ethanolamine (virodhamine), and N-arachidonoyl-dopamine (NADA). The physiological functions for these compounds have not yet been established.
Endogenous (adj.) - Originating or produced within an organism, tissue, or cell. Caused by factors within the body.
Exogenous (adj.) - Originating or produced outside of an organism, tissue, or cell. Having a cause external to the body.
FAAH (abbr.) (n.) - Fatty acid amide hydrolase (FAAH) catalyzes the hydrolysis of anandamide. The expression of CB1 receptors and FAAH is increased in mature human adipocytes compared with that in preadipocytes. There is an association between an FAAH missense mutation and human obesity.
GABA (abbr.) (n.) - γ-aminobutyric acid. An amino acid in the central nervous system and that is associated with transmission of inhibitory nerve impulses.
Ghrelin (n.) - An orexigenic hormone produced by the stomach.
Glutamate (n.) - Glutamic acid. A neurotransmitter that inhibits neural excitation in the central nervous system.
GPCRs (abbr.) (n.) - G protein–coupled receptors. The family of G proteins that interact with GPCRs are predominately the heterotrimeric G proteins, which consist of 3 different subunits, α,β and γ. When the G protein complex interacts with an active receptor, the α subunit exchanges its bound GDP (guanosine diphosphate) for GTP (guanosine triphospate) (hence the “G” in G proteins), and dissociates from the β/γ dimmer. CB1 and CB2 receptors primarily couple to G proteins of the inhibitory G protein (Gi/o) class. The α subunits from these G proteins inhibit adenylyl cyclase.
GPR55 (n.) - An orphan G protein-coupled receptor expressed in brain and various peripheral tissues in humans and rats. Several cannabinoid agonists bind to and activate the receptor GPR55.
Hepatic steatosis (n.) - Yellow discoloration of the liver due to fatty degeneration of the parenchymal cells.
Heterodimer (n.) - Protein complex composed of two different polypeptide chains.
Homeostasis (n.) - The ability or tendency of an organism or a cell to maintain internal equilibrium by adjusting its physiological processes.
Hydrolysis (n.) - Hydrolysis refers to the splitting of a compound into fragments by the addition of water, the hydroxyl group being incorporated in one fragment and the hydrogen atom in the other. The fatty acid amide hydrolase (FAAH) is the enzyme responsible for the hydrolysis of anandamide.
Hyperalgesia (n.) - Extreme sensitivity to pain.
Hyperphagia (n.) - Abnormally increased consumption of and appetite for food.
In vitro (adj.) - Latin for “in glass.” Taking place in an isolated cell-free extract. Also refers to cells growing in culture (in vitro) as opposed to in an organism (in vivo).
In vivo (adj.) - Latin for “in life.” In an intact cell or organism.
Insulin resistance (n.) - A state of diminished effectiveness of insulin in lowering the levels of blood sugar.
Knockout mice (n(pl).) - Informal term for the generation of mice in which the function of a particular gene product has been completely eliminated. For example, CB1 receptor knockout mice (CB1−/−) do not express functional CB1 receptor mRNA or protein.
Leptin (n.) - A 16-kDa–protein hormone that plays a key role in regulating energy intake and energy expenditure, including the regulation of appetite and metabolism.
Ligand (n.) - A ligand is any molecule that binds to a specific site on a protein or other molecule. For example, endocannabinoids are ligands for the CB1 and CB2 receptors.
Limbic system (n.) - A group of deep brain structures, common to all mammals. Includes the hippocampus, amygdala, gyrus fornicatus, and connecting structures. It is associated with olfaction, emotion, motivation, behavior, and various autonomic functions. The limbic system is believed to contain the neuronal circuitry that determines perceptions of food palatability and the “wanting and liking” of food.
Lipophilic (adj.) - Hydrophobic (literally, “water hating”). Describes a molecule (or part of a molecule) that is unable to dissolve in water.
MAGL (abbr.) (n.) - Monoacylglycerol lipase is the enzyme responsible for the degradation of the endocannabinoid 2-arachidonoylglycerol (2-AG).
MAPK (abbr.) (n.) - Mitogen-activated protein kinases (MAPK) are enzymes that perform crucial steps in relaying signals from the cell membrane to the nucleus. They are serine/threonine kinases, ie, they phosphorylate other proteins on serine/threonine residues. MAP kinases phosphorylate gene-regulatory proteins and other protein kinases. MAP kinases are usually activated only transiently in response to extracellular signals. Examples include extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinase (c-JNK), and p38 MAPK (p38). Activation of the CB1 and CB2 receptors can lead to activation of MAPK in some cell types.
Metabolism (n.) - Sum total of the chemical processes that take place in living cells.
Metabotropic Receptor (n.) - Metabotropic receptors are linked to GTP-binding (G) proteins. Receptors that form ion channels are ionotropic and those that are linked to G-proteins are metabotropic. Both ionotropic and metabotropic receptors are linked to multiple intracellular messengers, such as Ca2+ and cyclic adenosine monophosphate (cAMP). The CB1 receptor is a metabotropic receptor.
mRNA (abbr.) (n.) - (messenger RNA) An RNA (ribonucleic acid) molecule that specifies the amino acid sequence of a protein. It is translated into protein in a process catalyzed by ribosomes.
NAPE-PLD (abbr.) (n.) - acylphosphatidylethanolamine-selective phospholipase D is an anandamide synthetic enzyme.
N-arachidonoyl-dopamine (n.) - N-arachidonoyl-dopamine (NADA) is a newly proposed endocannabinoid. The biosynthetic mechanism of NADA is under study. Its physiological function has not yet been established.
Neuromodulatory (n.) - Neuromodulatory effects are produced by substances released by a neuron (other than neurotransmitters). These effects are characterized by the transmission of information to adjacent or nearby neurons, either enhancing or damping their activities. The endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) are produced by neuromodulatory effects in the brain.
Neuroprotection (n.) - Protection against neuronal injury or degeneration in the central nervous system following acute disorders (e.g. stroke or nervous system injury/trauma) or as a result of chronic neurodegenerative diseases (e.g. Parkinson's, Alzheimer's, Multiple Sclerosis).
Neurotransmitter (n.) - Small signal molecule secreted by the presynaptic nerve cell at a chemical synapse. Relays signals to postsynaptic cells. Examples include acetylcholine, glutamate, and GABA.
Nociception (n.) - Pain sense.
Noladin (n.) - Noladin is a newly proposed endocannabinoid (noladin, 2-AGE). The biosynthetic mechanism of noladin is under study. Its physiological function has not yet been established.
Nucleus accumbens (n.) - A limbic forebrain area implicated in eating motivation. Dopaminergic axons project from the ventral tegmental area to the nucleus accumbens and the prefrontal cortex. This pathway is activated by the expectation of rewarding stimuli.
Orexigenic (adj.) - Increasing or stimulating the appetite.
Pair-feeding (adv.) - Feeding a group of animals or subjects the same amount and composition of food as a test group of animals or subjects.
Paracrine signaling (n.) - Short-range cell-cell communication via secreted signaling molecules that act on adjacent cells. Endocannabinoids act on cells in a paracrine or autocrine manner in peripheral tissues.
Phenotype (n.) - The observable character of a cell or an organism.
Phospholipid (n.) - Phospholipids are the main category of lipid molecules used to construct biological membranes. Phospholipids are generally composed of two fatty acids linked through glycerol phosphate to one of a variety of polar groups. The endocannabinoids anandamide and 2-arachidonoylglycerol are synthesized via a phospholipid-dependent pathway.
PKA (abbr.) (n.) - Protein kinase A (cyclic AMP-dependent protein kinase). Enzyme that phosphorylates target proteins in response to a rise in intracellular cyclic AMP.
Polymorphism (n.) - Many different alleles of a gene, none of which is predominant in the population.
Prodrug (n.) - A prodrug is a pharmacological substance (drug) that is administered in an inactive (or significantly less active) form. Once administered, a prodrug is metabolized in the body into the active compound.
Retrograde signaling (n.) - The communication by signaling molecules derived from postsynaptic and delivered to presynaptic structures (opposite to the direction of travel of conventional neurotransmitters).
Rimonabant (n.) - Rimonabant is a selective CB1 receptor antagonist. The safety and efficacy of rimonabant has been demonstrated in Phase III clinical trials. The chemical name is N-piperino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide.
Signaling molecule (n.) - Extracellular or intracellular molecule that cues the response of a cell to the behavior of other cells or objects in the environment.
SREBP-1c (abbr.) (n.) - Sterol regulatory element-binding protein-1c is a transcription factor. A primary molecular pathway for hepatic lipogenesis involves activation of SREBP-1c.
Subcutaneous adipose tissue (n.) - Adipose tissue between the fascia of skin and the muscles.
THC (abbr.) (n.) - Δ9-tetrahydrocannabinol (THC) is the major pharmacologically active constituent of Cannabis sativa.
TRPV1 receptor (abbr.) (n.) - Transient receptor potential vanilloid (TRPV1) receptor. The vanilloid type 1 receptor. It is the site of action of capsaicin, and is also activated by the endocannabinoid anandamide.
Virodhamine (n.) - Virodhamine (O-arachidonoyl-ethanolamine) is a newly proposed endocannabinoid. The biosynthetic mechanism of virodhamine is under study. Its physiological function has not yet been established.
Visceral adipose tissue (n.) - Adipose tissue surrounding the organs, or viscera, in the thorax, abdomen, and pelvis. There is a strong, positive correlation between the amount of visceral adipose tissue and the health risks of obesity.
VTA (abbr.) (n.) - Ventral tegmental area. Dopaminergic axons project from the VTA to the nucleus accumbens and the prefrontal cortex. This pathway is activated by the expectation of rewarding stimuli.
Wild-type (adj.) - Normal, nonmutant form of an organism; the form found in nature (in the wild). For example, wild-type mice are genetically normal.
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