Signaling Lipids

Question 1

Signaling lipids are responsible for regulating what important process?

Answer 1

Inflammatory response

Question 2

What is AA and why is it important?

Answer 2

AA or arachidonic acid is a precursor to numerous bioactive lipids

Question 3

What enzymes are responsible for converting AA to prostaglandins?

Answer 3

Cox-1 and Cox-2 convert AA into prostaglandin H2 (PGH2)

Question 4

Cox-1

Answer 4

Expressed in most tissues

Question 5

Cox-2

Answer 5

Expression of this enzyme increases during inflammation

Question 6

What is prostaglandin E2 (PGE2)

Answer 6

• Synthesized by the enzyme prostaglandin E synthase (PGES-1) from PGH2
• Plays multiple roles during inflammation / sickness including:
• Pain
• Swelling
• Fever
• Appetite suppression

Question 7

How does PGE2 exert fever symptoms?

Answer 7

• PGE2 activates 4 distinct receptors (EP1-EP4)
• EP1, EP2, EP4 = activators
• EP3 = inhibitor

Question 8

What are nociceptors?

Answer 8

Specialized nerves that transmit panful stimuli from the site of inflammation to the spinal cord

Question 9

How does inflammation affect nociceptors?

Answer 9

Inflammation increases nociceptor activity and enhances pain

Question 10

How does PGE2 increase nociceptor activity?

Answer 10

PGE2 activates EP2 and EP4 receptors

Question 11

How can you stop fever symptoms?

Answer 11

• Cox inhibitors
• Prostaglandins are synthesized by Cox-1 and Cox-2 during inflammation (prostaglandins induce fever symptoms)
• Inhibition of Cox reduces pain, inflammation, and fever

Question 12

What are some examples of Cox inhibitors?

Answer 12

• Aspirin
• Ibuprofen

Question 13

What are some effects of Cox inhibitors?

Answer 13

• Gastrointestinal ulcerations
  Cox-1 protects gastric mucosa from gastric acid

Question 14

What has been used in place of Cox inhibitors in order to suppress fever symptoms?

Answer 14

• Therapeutic targeting of PGES-1 (enzyme that produces PGE2)
• Inhibition of PGES-1 reduces levels of PGE2 without affecting the synthesis of prostacyclins

Question 15

What are leukotrienes

Answer 15

Bioactive lipids synthesized from AA

Question 16

What are neutrophils?

Answer 16

Immune cells that destroy invading pathogens

Question 17

What is the significance of leukotriene B4 (LTB4)

Answer 17

Promotes neutrophil chemotaxis (movement towards the site of infection)
This is how neutrophils know where to go

Question 18

What is the significance of cysteinyl leukotrienes CysLT1?

Answer 18

• Contribute to asthma
• Activation of CysLT1 induces airway vasoconstriction
• CysLT1 blockers = used to prevent asthma symptoms