Eicosanoids

Question 1

Types of Eicosanoids

Answer 1

Prostaglandins, Thromboxanes, & Leukotrienes

Question 2

Eicosanoid signaling pathway

Answer 2

Eicosanoids act locally through G-protein linked signal pathways leading to either increased cAMP or intracellular Ca+

Question 3

Role of Phosphatiylinositol Bis-phosphate (PIP2) and Phospholipase A2 in Eicosanoid production

Answer 3

Phospholipase C will cleave PIP2 to generate IP3 and DAG for cell signaling

However -

Phospholipase A2 cleaves PIP2 and forms Arachidonic Acid and Lyso-PIP2

Arachidonic Acid is a precursor of prostaglandins and thromboxanes

Phopholipase A2 is inhibited by Cotisol

Question 4

Cycooxygenase

Answer 4

COX 1 & 2

Forms Prostaglandin G2 from Arachidonic Acid

PGG2 is a precursor of both Prostacyclin (PGI2) and Thromboxane (TXA2)

COX1 inhibited by ASA and NSAIDS
COX2 inhibited by Corticosteroids and NSAIDS

COX2 induction leads to increased prostaglandin synthesis

Question 5

Prostacyclin (PGI2)

Answer 5

Produced primarily by endothelium of vessels
Vasodilation
Inhibits platelet aggregation

Question 6

Thromboxane (TXA2)

Answer 6

Produced primarily by platelets
Vasoconstriction
Promotes platelet aggregation

Question 7

Synthesis of Prostacyclin (PGI2)

Answer 7

Arachidonic Acid forms PGG2 via COX

PGG2 forms PGH2 via peroxidase

PGH2 forms PGI2 via prostacyclin synthase

Question 8

Synthesis of Thromboxane

Answer 8

Arachidonic Acid forms PGG2 via COX

PGG forms PGH2 via peroxidase

PGH2 forms TXA2 via thromboxane synthase

Question 9

Synthesis of Leukotrienes

Answer 9

Arachidonic Acid forms 5-HPETE via 5-lipoxygenase

5-HPETE forms LTA2

LTA2 is used in mast cells and eosinophils to form LTC2 by addition of the tripeptide GSH (glutathione)

Successive cleavage of glutamate and glycine lead to LTD and LTE, respectively

Question 10

Cysteinyl-leukotrienes

Answer 10

LTC2 through LTF2 contain either a peptide or cysteine in their structure.

Released during anaphylaxis, are components of the slow-reacting substance of anaphylaxis (SRS-A). Much more potent than histamine.

LTC, LTD and LTE increase vascular permeability but also lead to severe bronchoconstriction, vasoconstriction and lung edema.

Question 11

Drugs that are most selective at inhibiting SRS-anaphylaxis

Answer 11

Benoxaprophen and Zileuton

Question 12

Drugs that inhibit Thromboxane Synthase

Answer 12

Dazoxiben and Dipyramidole