86. Eicosanoids

Question 1

Autacoids

Answer 1

Every cell releases chemical signals. Mainly those of the diffuse endocrine system (Diffuse Neuro- Endocrine System, DNES) function like this. Their products (signals) were named as autacoids.

They can be chemically divided into two groups: peptides and fatty acid-like substances.

Question 2

Site of eicosanoid production

Answer 2

It is produced everywhere in the body

Every cell is able to produce

Question 3

Eicosanoid synthesis

Answer 3

20-C FA’s. Controlled synth. from phospholipids via enzymatic steps
Mediated by G protein → activates PLA2 enzyme

MPL (membrane phospholipids) = PLA2 substrates
HPETE (hydroxy-peroxy-eicosa-tetraenoic acid), Lipoxins, HETE (Hydroxy-eicosa-tetranenoic acid), leukotrienes

Question 4

common feature

Answer 4

• Their common feature is that they are quickly degraded after entering the plasma.
• Their plasma concentration is fairly low. They mostly act locally or through a paracrine way.
• Although they are lipid soluble, they bind to surface membrane receptors and elicit G protein dependent transduction.

Question 5

Effects – increasing inflammation

Answer 5

Prostaglandins and leukotrienes are both involved in initiation of inflammation.

Question 6

Effects – insulin release

Answer 6

• still not entirely elucidated eicosanoid action-mechanism is the effect on insulin release of B cells. HPETE (lipoxygenase pathway) stimulates, PGE2 (cyclooxygenase pathway) inhibits insulin release.

Question 7

Effects – bone resorption

Answer 7

PGE2, produced by the osteoblast cellular line, has a parathyroid hormone-like effect on calcium mobilization from the bone: it increases calcium permeability in the osseous interstitial side, making possible the entry of calcium into the plasma.

Question 8

Effects – reproduction

Answer 8

Precondition of luteolysis is PGF2-alpha prod.

Question 9

Effects – thrombocyte

Answer 9

Enothelial cells (in mouse) release PGI & NO → induce G protein mediated incr. of cAMP. IC cAMP inhibits PLA2 enzyme → no thromboxane → no platelet aggregation. TXA2 synth in platelets increases → increase aggregation.

Question 10

Effects – kidney

Answer 10

Prostatcyclin synthesis in renal tubule cells enhances renin secretion, increases RPF, and antagonizes the effect of ADH.

Question 11

Regulation

Answer 11

• Corticosteroids, Mepacrine inhibit the entire eicosanoid synthesis. This is one cause of the anti-inflammatory effect of glucocorticoids.
• Salicylic acid, Indomethacin, Ibuprofen specifically inhibits cyclooxygenase enzyme. Since it does not inhibit lipoxygenase pathway, it does not have any influence on the communication between leukocytes (LT, LX, etc.).
• Benzidamine, Imidazol specifically inhibit thromboxane synthase enzyme. By applying it, normal production of prostaglandins (reproductive processes) is not blocked, but the synthesis of thromboxane decreases. (E.g., the aggregation of platelets can be effectively decreased this way!)