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

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