Lecture 11: Arachidonic Acid Pathway

Question 1

Eicosanoids are products of oxygenation of…

Answer 1

Polyunsaturated long-chain fatty acids, including arachidonic acid (most abundant eicosanoid precursor), released from membrane

Question 2

Products of the COX pathway

Answer 2

Prostaglandins, prostacyclin, thromboxane

Question 3

Effects of prostaglandins on vascular SM

Answer 3

Vasoconstrictors (TXA2 and PGF2alpha) AND vasodilators (PGI2 and PGE2)

Question 4

PGI2

Answer 4

Vasodilation and inhibition of SM proliferation

Question 5

TXA2

Answer 5

Vasoconstriction and SM mitogen

Question 6

COX1 and COX2

Answer 6

COX1 = found in all tissues, especially in GI; COX2 = upregulated in kidney, GI, CNS, endothelium

Question 7

Contraction of longitudinal, circular muscles in GI tract

Answer 7

PGF2 (also causes vasoconstriction)

Question 8

Relaxation of circular muscles

Answer 8

PGE2 (also causes vasodilation)

Question 9

Contraction of respiratory SM

Answer 9

TXA2, PGF2alpha

Question 10

Relaxation of respiratory SM

Answer 10

PGE2, PGI2

Question 11

Inhibit platelet aggregation

Answer 11

Higher concentration of PGE2, PGD2, PGI2

Question 12

TXA2 and platelets

Answer 12

Directly enhances platelet aggregation and augments other platelet agonists (thrombin)

Question 13

Vasodilation in kidney: mediators, where, and effect on GFR

Answer 13

Most in afferent arteriole, PGE2 and PGI2, increase GFR (GOOD)

Question 14

PGE2 and PGI2 stimulates ________ release. Results in?

Answer 14

Renin –> increased AII –> constricted efferent arteriole –> increased hydrostatic pressure –> increase GFR (GOOD)

Question 15

TXA2 and the kidney

Answer 15

Renal constriction (mostly afferent) –> decreased GFR

Question 16

Net effect of eiconsanoids on GFR is to ___________ GFR

Answer 16

Increase (TXA2 not as strong)

Question 17

PGE2 and PGI2 effect on Na+ and water

Answer 17

Increases Na+ excretion (via decreased Na+ resaobsorption) and increases water excretion (via attenuated ADH)

Question 18

PGE2 and PGI2 effect on blood pressure via excretion

Answer 18

Maintains a low blood pressure

Question 19

What is the net of effect of prostaglandins on BP? What are the two things behind this balance?

Answer 19

Decrease BP: PGE2 and PGI2 –> balance b/t Na+ and H2O excretion (decrease BP) VS increase in renin (increase BP)

Question 20

What prostaglandins increase body temperature? Why does this make sense?

Answer 20

PGE2, PGF2alpha, PGI2; NSAIDs are FEVER REDUCERS

Question 21

Effects of PGE on neurotransmission

Answer 21

PGE inhibit release of NE from sympa postganglionic nerve endings, leading to LESS VASOCONSTRICTION

Question 22

Two reasons that COX inhibition causes vasoconstiriction

Answer 22

Leads to NE release AND inhibit synthesis of vasodilators (PGE2 and PGI2)

Question 23

Peripheral nerve endings are sensitized to pain by…How?

Answer 23

PGE2 and PGI2; increased membrane excitability

Question 24

Prostaglandins effects on CNS pain modulation (3)

Answer 24

Increase excitability of spinal dorsal horn neurons, augment pain intensity, widen pain perception area

Question 25

Effects of PGE2 and PGI2 on inflammation

Answer 25

Increase vascular permeability and leukocyte infiltration

Question 26

Prostaglandins in the eye…

Answer 26

PGE and PGF derivatives lower intra ocular pressure (Latanoprost)

Question 27

LOX pathway creates what? What do these do (main, opposing actions)?

Answer 27

HETEs, leukotrienes, lipoxins; Leukotrienes: Potent chemoattractants for eos and T-cells –> inflammation; Lipoxins: activate macrophages, inhibit eos, lymphocytes

Question 28

Leukotrienes are a product of the LOX pathway. Importance for airways?

Answer 28

Bronchoconstrictors –> bronchoconstriction, increased permeability, and increased mucus secretion

Question 29

NSAIDs and airways

Answer 29

10% of patients taking NSAIDs have bronchospasm likely from shifting arachidonate metabolism from COX to the leukotriene arm

Question 30

Cytochrome P450/EET and LOX pathways on the heart

Answer 30

LOX –> proliferation of SM In vascular, decreased coronary blood flow, decreased contractility; EET –> vasodilation of cardiac vessels