Eicosanoids and Cannabinoids

Eicosanoids

Biologically active lipids derived from arachidonic acid (C20 polyunsaturated fatty acid); act as local mediators in inflammation and physiology; not stored in cells.

Arachidonic Acid

A 20-carbon polyunsaturated fatty acid that serves as a precursor for eicosanoid synthesis.

Prostanoids

A group of eicosanoids including prostaglandins, thromboxanes, and prostacyclins derived via the cyclooxygenase (COX) pathway.

Cyclooxygenase (COX)

Enzyme that converts arachidonic acid to prostaglandin H2 (PGH2); exists as (constitutive) and inducible) forms

COX-1

Constitutively expressed enzyme producing prostanoids for normal physiological functions like gastric protection and platelet aggregation.

COX-2

Inducible enzyme expressed during inflammation, generating prostanoids involved in pain, fever, and inflammation.

Prostaglandins (PGs)

Lipid mediators regulating inflammation, vascular tone, platelet function, gastric protection, and uterine activity.

Thromboxanes (TXs)

Eicosanoids produced by platelets promoting vasoconstriction and platelet aggregation.

Prostacyclin (PGI2)

Produced by endothelial cells; inhibits platelet aggregation and causes vasodilation.

Leukotrienes (LTs)

Eicosanoids synthesized via the 5-lipoxygenase pathway in leukocytes; key mediators in inflammation and asthma.

Epoxyeicosatrienoic acids (EETs)

Eicosanoids formed via cytochrome P450 epoxygenase pathway; regulate vascular tone and inflammation.

Lipoxins

Anti-inflammatory eicosanoids formed via lipoxygenase pathways.

Phospholipase A2 (PLA2)

Enzyme that releases arachidonic acid from membrane phospholipids.

NSAIDs

Non-steroidal anti-inflammatory drugs that inhibit COX enzymes to reduce prostaglandin production, thereby decreasing pain, fever, and inflammation.

DP Receptor

G-protein-coupled receptor (GPCR) for PGD2; causes vasodilation and inhibits platelet aggregation.

EP Receptor

GPCR for PGE2; mediates inflammation, fever, vasodilation, gastric protection, and uterine effects.

FP Receptor

GPCR for PGF2α; stimulates uterine contraction (used in labor induction and glaucoma treatment).

IP Receptor

GPCR for PGI2; causes vasodilation and inhibits platelet aggregation.

TP Receptor

GPCR for TXA2; induces vasoconstriction and platelet aggregation.

LTB4

Leukotriene that attracts neutrophils and promotes inflammatory cytokine release.

Cysteinyl Leukotrienes (LTC4, LTD4, LTE4)

Cause bronchoconstriction, vasodilation, and mucus secretion; involved in asthma pathophysiology.

CysLT Receptor

Receptor for cysteinyl leukotrienes; antagonized by drugs like montelukast and zafirlukast to treat asthma.

Cannabinoids

Compounds derived from Cannabis sativa; include psychoactive THC and non-psychoactive CBD.

Δ9-Tetrahydrocannabinol (THC)

Main psychoactive compound in cannabis; produces relaxation, altered perception, and analgesia.

Cannabidiol (CBD)

Non-psychoactive cannabinoid with potential anxiolytic, anti-inflammatory, and anti-epileptic effects.

Cannabinol (CBN)

A mildly psychoactive degradation product of THC.

CB1 Receptor

Cannabinoid receptor primarily in the brain; inhibits neurotransmitter release and modulates motor control, memory, and appetite.

CB2 Receptor

Cannabinoid receptor found mainly on immune cells; modulates immune responses and inflammation.

Endocannabinoids

Endogenous cannabinoids synthesized from membrane lipids; act as retrograde neuromodulators.

Anandamide (AEA)

An endocannabinoid ligand for CB1/CB2 receptors; involved in mood, pain, and appetite regulation.

2-Arachidonyl Glycerol (2-AG)

Another key endocannabinoid acting on CB1/CB2 receptors.

Retrograde Signalling

Neuronal communication where signals travel from postsynaptic to presynaptic neurons to modulate neurotransmitter release.

Nabiximols

Pharmaceutical mixture of THC and CBD used to treat chronic pain and multiple sclerosis symptoms.

Nabilone

Synthetic cannabinoid used for chemotherapy-induced nausea and vomiting.

Synthetic Cannabinoids

Lab-made compounds mimicking THC effects; some used therapeutically, others as recreational drugs (“legal highs”).

Gi/o Protein Coupling

Mechanism by which CB1/CB2 receptors inhibit adenylate cyclase and reduce Ca2+ influx, causing neuronal inhibition.

Adenylate Cyclase Inhibition

Reduces cAMP formation, leading to decreased neurotransmitter release and cellular activity.