prostaglandins - notes

Question 1

prostaglandins

Answer 1

active principle in human serum that induced rhythmic contraction and relaxation of myometrium
produced in highest concentration in seminal vesicles
metabolic products of unsaturated membrane FA

Question 2

eicosanoids

Answer 2

metabolic products of unsaturated membrane FA (the 20-carbon eicosaenoic acids)
includes prostaglandins, leukotrienes, thromboxanes
produced by virtually all cells
synthesized and released in response to inflammatory, mechanical, neurological, or hormonal stimuli
degraded by dehydrogenase enzymes, most effectively in lung
short half lives so local - autocrine or paracrine

Question 3

nomeclature of eicosanoids

Answer 3

letters designate ring structure

numbers denote number of double bonds - important for receptor binding and function

Question 4

receptors for eicosanoids

Answer 4

usually g-protein coupled

specific for each eicosanoid - each can have multiple

Question 5

production of eicosanoids

Answer 5

produced by virtually all cells
different cells make different ones
precursors = unsaturated membrane FA, primarily arachidonic acid
stimuli activate phospholipase A2 family => release of membrane FA (eicosaenoic acids)
prostaglandins and thromboxanes are formed via cyclooxygenase (COX) pathways
leukotrienes produced via enzyme 5-lipoxygenase
lipoxins products of 5, 12, adn 15- lipoxygenases

Question 6

cyclooxygenase (COX)

Answer 6

makes prostaglandins and thromboxanes

Question 7

5-lipoxygenase

Answer 7

makes leukotrienes and lipoxins

Question 8

5-, 12- and 15-lipoxygenases

Answer 8

make lipoxins

Question 9

inflammatory signals and eicosanoids

Answer 9

inflammatory signals induce expression of COX-2
activate phopholipase A2 in many cell types
=> eicosanoid production at sites of inflammation

Question 10

eicosanoids and pain

Answer 10

hyperalgesic - don’t produce pain directly, but increase tissue sensitivity to other stimuli

Question 11

e-protaglandins

Answer 11

induce hyperalgesia via EP4

Question 12

eicosanoids and edema

Answer 12

enhance the edema caused by bradykinin, histamine, adn teh C5a anaphylaatoxin

Question 13

cox-2

Answer 13

makes prostaglandins

Question 14

eicosanoids and immune response

Answer 14

contribute to leukocyte activation and chemostaxis

e.g.: LTB4 is chemotaxic for both T cells and PMNs

Question 15

eicosanoids in asthma

Answer 15

cysteinyl leukotrienes induce abnormalities in asthma
eg cysLTs; LTC4; D4; E4
1: induce SM contraction and protracted bronchoconstriction
2: promote microvascular permeability, bronchovascular leakage, mucous secretion
3: promote leukocyte infiltration and production of proinflammatory cytokines

therefore 5-lipoxygenase inhibitors and leukotriene receptor anatagonists are effective anti-asthma drugs

Question 16

inhibitors of eicosanoid production

Answer 16

NSAIDs
coxibs (COX2 inhibitors)
glucocorticoids

Question 17

things that counter inflammatory effects of leukotrienes

Answer 17

lipoxins, resolvins, protectins

Question 18

eicosanoids in platelet function (summary card)

Answer 18

1: thromboxane A2 released by platelets via COX-1 => stimulates platelet aggregation and vasoconstriction
2: prostacyclin produced by vascular endothelial cells via cox1 and cox2 inhibits platelet aggregation and causes vasodilation
3: aspirin inhibits cox1 and cox2 => impaired thromboxane production
4: endothelial cells, via synthesis of new cox 1 and cox2, can produce protacyclin once aspirin levels decline

Question 19

thromboxane A2

Answer 19

released by platelets via cox1

stimulates platelet aggregation and vasoconstriction

Question 20

prostacyclin (PGI2)

Answer 20

produced by vascular endotehlial cells via cox-1 and cox-2

inhibits platelet aggregation and causes vasodilation

Question 21

aspirin in platelet function

Answer 21

unlike other nsaids, aspirin irreversibly inhibits cox1 and cox2
anucleate platelets can’t make new Cox1, so thromboxane production impaired
once aspirin levels decline, endothelial cells can synthesize new cox1 and cox1 and make prostacyclin

Question 22

ductus arteriosus patency

Answer 22

maintained in the fetus by locally produced and circulating I and E prostaglandins

Question 23

indomethacin and ibuprofen on eicosanoids

Answer 23

can reduce blood flow through ductus arteriosus within 24 hours
eliminate need for surgery in many premature infants

Question 24

E and I protaglandins

Answer 24

reduce areterial blood pressure by direct vasodilator action on resistance vessels, modulation of norepi release, modulation of renal hormones

Question 25

atherogenesis

Answer 25

5-lipoxygenase gene polymorphisms are linked to coronary occlusion omega-3 FA rich diet decreases cardiovascular disease = thromboxane B3 is inactive and PGI3 is active

Question 26

aspirin in cardiovascular physiology

Answer 26

low dose aspirin can reduce arterial thrombosis

Question 27

coxibs

Answer 27

cox-2 inhibitors | can increase thrombosis by selectively inhibiting prostocyclin but not thromboxane

Question 28

eicosanoids in reproductive physiology

Answer 28

1: PGE2 and PGF2 essential for follicular rupture 2: also induce cervical softening/dilation and uterine contractions 3: PGE2 induces penile erection 4: NSAIDs can prolong gestation and are sometimes effective in arresting premature labor 5: e-prostaglandins can be used for termination of both early and late pregnancies

Question 29

eicosanoids and renal physiology

Answer 29

1: PGI2 and PGE2 are normally low but are increased by angiotensis II, norepi and vasopressin 2: maintain renal blood flow through direct renal vasodilatory action 3: PGs antagonize hydroosmotic and vacular effects of ADH 4: I and E have positive role in baroreceptor induced renin release

Question 30

eicosanoids and the gut

Answer 30

PGE>>PGA>PGI in decreasing acidity, stimulating bicarbonate and mucous secretion by epi cells, and protecting the gastric mucosa

Question 31

misoprostol

Answer 31

e prostaglandin analog useful for protection against gastric ulcers in high-risk groups s.a. patients receiving NSAID therapy for arthritis and other inflammatory diseases

Question 32

NSAIDs and the gut and eicosanoids

Answer 32

inhibit PG ability to decrease acidity, stimulate bicarbonate and mucous secretion, and protect gastric mucosa decrease frequency of colorectal polyps, but increase frequency of gastric ulcers

Question 33

TXA2 causes:

Answer 33

1: platelet aggregation (thrombosis formation) 2: vasoconstriction 3: bronchoconstriction 4: may promote atherosclerosis

Question 34

PGI2 causes:

Answer 34

1: antiaggregation (throbolysis) 2: vasodilation 3: coronary blood flow (patent ductus arteriosus) 4: GI protection

Question 35

PGE1, PGE2, PGF2alpha cause:

Answer 35

1: GI protection 2: hyperalgesia 3: cervical dilation 4: uterine contraction (high in dysmenorrhea) 5: fever 6: immune regulation 7: may reduce atherosclerosis 8: penile erection 9: vasodilation

Question 36

LTC4, LTD4, LTE4

Answer 36

1: increase vascular permeability 2: smooth muscle contraction 3: vasoconstriction 4: bronchoconstriction

Question 37

LTB4 causes

Answer 37

1: leukocyte chemotaxis 2: leukocyte adhesion 3: increase vascular permeability