Inflammation Mediators and Drugs

Question 1

Histamine

Answer 1

Redness, heat, swelling, and airway constriction. (no chemotaxis)

Found in most tissues especially lung, skin, and stomach.

Stored in preformed granules in mast cells and basophils. Ionically bonded to a heparin-protein complex.

Also non mast-cell form. (unsure function)

Histamine is synthesized from histidine by L-histidine decarboxylase.

Systemic effects: redness, flare, local edema, nasal symptoms, itching, and more.

Four Receptors: H1, H2, H3, and H4

Question 2

PGE 2

Answer 2

Vasodilate, increase vascular permeability, and cause pain. Fever.

Question 3

PGI 2

Answer 3

Vasodilate, increase vascular permeability, and cause pain. Also opposes platelet aggregation.

Question 4

TXA 2

Answer 4

Causes platelet aggregation and vasoconstriction.

Question 5

PGD

Answer 5

Bronchoconstriction

Question 6

Thromboxane

Answer 6

Vasoconstriction. Bronchoconstriction. and platelet aggregation.

Question 7

LTB4

Answer 7

Chemotactic (PMNs) and reduces pain threshold.

Question 8

Peptido lekotrienes

Answer 8

Bronchoconstriction, increased vascular permeability, and chemotaxis (eosinophils)

Question 9

Kinins (Bradykinin and kallidin)

Answer 9

Very strong vasoldilator with resulting hypotension. Not a major chemotactic agent. (Also does “everything” according to Regal)

Acted on by two key enzymes: Kinase I (Carboxypeptidase N) and Kinase II (Angiotensin Converting Enzyme).

More potent w/o terminal des-arg which are cleaved by kinase I and kinase II.

Question 10

H1 receptor

Answer 10

Histamine binding causes:

• bronchoconstriction
• GI contraction
• Increased vascular permeability (wheal)
• Pruritis
• Release of catecholamines from adrenal medulla

Question 11

H2 receptor

Answer 11

Histamine binding causes:

• gastric acid secretion
• inhibition of IgE-mediated basophil histamine release (negative feedback)
• inhibition of T cell cytotoxicity
• suppression of Th2 cells and cytokines

Question 12

COX-1

Answer 12

Found in platelets

Constuitively expressed in most cells and is thought to protect the gastric mucosa

Question 13

COX-2

Answer 13

Induced

Not found in platelets.

Expressed constitutively in the brain and kidney, but can be induced by certain serum factors, cytokines and growth factors in other tissues and at sites of inflammation.

The more important isozyme in the production of prostaglandins and thromboxane in inflammation.

Question 14

LTC4, LTD4, and LTE4

Answer 14

“peptide leukotrienes”

Interact with Cys LTR1 to cause:
-bronchoconstriction, eosinophil chemotaxis, inceased vascular permeability, increased mucous production,

Important for asthma.

Question 15

Histidine decarboxylase

Answer 15

Enzyme that converts Histidine to histamine

Found in mast cells and basophils.

Question 16

Kalikrein

Answer 16

Makes bradykinin and kallidrein. Found in plasma and causes vasodilation.

Question 17

Carboxypeptidase N

Answer 17

AKA kininase I or anaphylotoxin inactivator.

Removes the carboxy terminal arginase.

Works on on kinins, but also anything with a terminal arginine (enkephalins and C1 and C3)

Question 18

Angiotension Converting Enzyme

Answer 18

Same as kininase II or dipeptide hydrolase.

Degrades bradykinin (a potent vasodialotor). Causes an increase in blood pressure.

Also converts Angiotension I to Angiotension II (vasoconstrictor)

ACE inhibitors are antihypertesnsives from both mechanisms.