Eicosanoid Actions

Eicosanoids, or icosanoids function as autocrine and paracrine mediators, and are oxygenated hydrophobic derivatives of 20-carbon polyunsaturated essential fatty acids, predominantly arachidonic acid (AA) in humans.

Dihomo-gamma-linolenic acid (DGLA) and eicosapentaenoic acid (EPA, icosapentaenoic acid, timnodonic acid) also serve as eicosanoid precursors. Eicosanoids include leukotrienes with four double bonds and prostanoids with two double bonds (prostaglandins and prostacyclins with five-membered rings, and thromboxanes with heterocyclic oxane structures).

Eicosanoid	Secreting cells	Physiological functions
Prostaglandins
PGD2	mast cells	inhibition of platelet and leukocyte aggregation, reduction of T cell proliferation and lymphocyte migration, secretion of IL-1α and IL-2; vasodilation, and production of cAMP [↓coag, ↓imm, ↓cyt, ↑v, ↑cAMP * ]
PGE2	kidney, spleen, heart	vasodilation, cAMP production, increases effects of bradykinin and histamine in inflammatory response, induction of GI and uterine contractions, platelet aggregation; decreases T cells proliferation, lymphocyte migration, secretion of IL-1α and IL-2 [↑v, ↑ infl, ↑imm, ↓cyt * ]
PGF2α	kidney, spleen, heart	vasoconstriction, bronchoconstriction, and smooth muscle contraction [↓v, ↓br, ↓sm * ]
PGH2	many tissues	short-lived precursor to thromboxanes A2 and B2; platelet aggregation, and vasoconstriction [↑coag, ↓v]
PGI2 prostacyclin	heart, vascular endothelial cells	inhibits platelet and leukocyte aggregation, decreases T cell proliferation and lymphocyte migration and secretion of IL-1α and IL-2; vasodilation, cAMP production [↓coag, ↓imm, ↓cyt, ↑v * ]
Thromboxanes
TXA2	platelets	induces platelet aggregation, vasoconstriction, lymphocyte proliferation, and bronchoconstriction [↓v, ↑coag, ↑imm, ↑br * ]
TXB2	platelets	vasoconstriction [↓v * ]
Leukotrienes
LTB4	granulocytes, phagocytes, and epithelial cells	leukocyte chemotaxis and aggregation, vascular permeability, T cell proliferation, and secretion of IFNγ , IL-1 and IL-2 [↑inf, ↑vp, ↑imm, ↑cyt * ]
LTC4	granulocytes, phagocytes, and epithelial cells	component of slow-reactive substance of anaphylaxis (SRS-A), increases vasodilation, vascular permeability, bronchoconstriction, secretion of IFNγ [↑an, ↑v, ↑vp, ↓br, ↑cyt * ]
LTD4	granulocytes, phagocytes, and epithelial cells	predominant component of SRS-A, induces vasodilation, vascular permeability, bronchoconstriction, secretion of IFNγ [↑an, ↑v, ↑vp, ↓br, ↑cyt * ]
LTE4	mast cells and basophils	component of SRS-A, induces vasodilation and bronchoconstriction [↑an, ↑v, ↓br * ]
Physiological function of eicosanoids in various tissues
tissue	physiological function
inflammatory response	fever: PGEs act on thermoregulatory center in brain → increased body temperature (fever) pain: PGs → sensitize pain receptors to stimulation → increased pain PGs promote vasodilation & increased vascular permeability
intestinal smooth muscle	PGF2 & PGI2 → smooth muscle contraction → cramps PGE → decreased gastric acid secretion & ulceration
kidneys	PGE regulates arteriolar tone, compensatory vasodilatation, maintains normal blood flow, increased glomerular filtration rate
platelets	PGE1 & PGI2 → decreased platelet aggregation TXA2 increased platelet aggregation
pulmonary smooth muscle	PGI2 & PGE2 vasodilation & constriction, respectively TXA2 is a vasoconstrictor & bronchoconstrictor, PGFs contract while PGEs relax respiratory smooth muscle
reproductive organs	PGE2 & PGF2α → uterine contractions initiate & stimulate labor; dysmenorrhea
vascular smooth muscle	PGEs & PGI2 → smooth muscle dilation → vasodilation PGF2α; TXA2 → vasoconstriction

* ↑an = anaphylactic mediators, ↑br = bronchodilation, ↓br = bronchoconstriction, ↑/↓ coag = clotting enhanced/inhibited, ↑/↓cyt = cytokine secretion increased/decreased , ↑/↓imm = immune response increased/decreased, ↑/↓infl = inflammatory response increased/inhibited, ↑v = vasodilation, ↓v = vasoconstriction, ↑vp = vascular permeability increased

lipoproteins

	Density (g/ml)	protein %	TAG %	Function
chylomicron	<0.95	2	86	transport TAGs and cholesterol from intestine to other tissues
VLDL	0.95-1.006	8	55	transport TAGs from liver
IDL	1.006-1.019	15	31	converted from VLDL by lipase
LDL(bad)	1.019-1.063	22	6	converted from IDL by lipase--transport of cholesterol
HDL(good)	1.063-1.210	40-55	4	scavenge cholesterol; bring to liver

saturation of triacylglygerols

	Carbons:Unsaturation
Palmitate	16:0
Stearate	18:0
Palmitoleate	16:1 - cis at C9
Oleate	18:1 - cis at C9
Linoleate	18:2 - cis at C9 and C12
Linolenate	18:3 - cis at C9, C12 and C15