Histamine Receptors

Question 1

Where is histamine found

Answer 1

Mainly in mucosal and connective tissue type mast cells
Found in enterochromaffin-like cells and has endocrine function in gastric mucosa
Found in hypothalamic neurones in the CNS
Found in exogenous sources like nettles and food which is not well absorbed after digestion

Question 2

Histamine synthesis

Answer 2

Histidine -(histidine decarboxylase)-> histamine

Question 3

Where is histamine stored

Answer 3

In mast cell granules:
Skin
Lungs
Gut
Nasal mucosa

Question 4

What is degranulation

Answer 4

Breaking down of mast cell granule

Question 5

What stimulates histamine

Answer 5

Mechanical injury
Chemicals
Drug reactions (opioids)
Allergy

Question 6

Types of histamine receptor

H1

Answer 6

Gq linked

Stimulates phospholipidase C

Question 7

Types of histamine receptor

H2

Answer 7

Gs linked

Stimulates adenylyl cyclase

Question 8

Types of histamine receptor

H3

Answer 8

Gi linked

Inhibits AC

Question 9

Types of histamine receptor

H4

Answer 9

Gi linked

Inhibits AC and activated PLC by BY subunits

Question 10

Physiological roles of histamine

Answer 10

Beneficial inflammation - supplies plasma to tissues and removes parasites from the gut due to histamine causing smooth muscle contraction
AIDS gastric acid secretion and ‘wakefulness’ in CNS
Allows immune cells to access and repair and area
Cause plasma to leave cells and enter tissues
Controls gastric acid so it is not overproduced and causes ulcers

Question 11

H1

Answer 11

Vasodilator of arterioles
Increased vascular permeability via endothelial contraction
Activation of sensory nerves causing pain and itching
Oedema forms due to plasma leaking out of cells and stimulation of neuropeptides causes spread of redness

Question 12

H2

Answer 12

Vasodilator in vascular smooth muscle which has limited significance in inflammation

Question 13

Cutaneous response to histamine

Answer 13

Flush: local vasodilation via H1 receptors on blood vessels
Wheal: oedema formation, endothelial cell contraction due to H1
Flare: sensory nerve action via H1, release of dilator neuropeptides that spread from sit of injury

Question 14

H4

Answer 14

Highly expressed on white blood cells for leukocyte chemotaxis and activation
They act on sensory nerves

Question 15

Drugs acting on H3

Answer 15

H3 receptor antagonists/inverse agonists inhibit histamine release from CNS via H3 autoreceptors, blocking central H3 receptors will enhance histamine release

Question 16

H3

Answer 16

H3 receptors have high nasal activity and are active without ligands
Ciproxifan is an inverse agonist that lowers H3 signalling even in the absence of an agonist they increase wakefulness
Negative feedback receptor so will ‘turn off’ when histamine is detected. If the receptor is blocked, more histamine is released

Question 17

Histamine action

Answer 17

Involved in control of gastric acid secretion
Released from enterochromaffin-like cells in the stomach wall
Acid secretion driven by activation of parietal cell H2 receptors