Histamine + others

Question 1

Function of NO in inflammation (2)

Answer 1

• vasodilator

- anti-bactericidal molecule (respiratory burst)

Question 2

What is iNOs and how it works

Answer 2

• enzyme that makes NO its only expressed during inflammation in macrophages
• once made binds to calmodulin regardless if calcium present or not

Question 3

How is the iNOS expression switched on

Answer 3

• switched on by pro-inflammatory cells PGE2, IL-1 and TNF alpha all act on NFKB (transcription factor)

Question 4

describe how NO produced kills bacteria

Answer 4

• reacts with super oxide anion makes peroxynitrite= respiratory burst
• peroxynitrite = oxidising agent damages DNA, its released into phagosome to kill bacteria

Question 5

what substance p

Answer 5

-11 amino neuropeptide released by sensory nerves when they are excited

Question 6

function substance P (3)

Answer 6

• neurogenic inflammation mediator –> pain transmitter sends signal to spinal cord and to surrounding cells in an antidromic way (goes opp direction)
• sensitises cells to bradykinin
• acts on mast cells cause histamine release –> vasodilation

Question 7

what is Histamine + how its made + broken down

Answer 7

• basic amine
• made from histidine + histidine decarboxylase
• broken down by N-methyl transferase or diamine oxidase.

Question 8

storage of histamine

Answer 8

• mast cells (skin, lungs, intestinal mucosa)
• platelets (in granules associated with heparin and aidic protein that neutralises histamine basic charge)
• basophils
• histaminergic neurones= used as transmitter
• ELC in gastric mucosa= used release acid

Question 9

triggers of release of histamine

Answer 9

• substance P
  -IgE which complexes with antigen
  -activated C3a, C5a complex
  all these increase intracell ca2+ this releases hist

Question 10

morphine with histamine

Answer 10

morphine triggers histamine release overdose –> anaphylactic reaction

Question 11

histamine in hypersensitivity 1 (allergy)

Answer 11

• antigen= promotes IgE release
• IgE binds mast cell via FC region
• re exposure - antigen binds to IgE = causes dimerisation of FC
• this increase intracelluar calcium in mast cell
• this triggers histamine release + also sersatonin

Question 12

modulation of histamine release

Answer 12

• omalizumab = antibody that binds to IgE prevents it binding to mast cells. expensive
• sodium cromglicate -mast cell stabilisers prevents granules releasing histamine

Question 13

types of histamine receptor H1 function

Answer 13

activates phospholipase C - increases calcium

• involved in broncho-constriction in lungs worsens asthma, struggle breathing anaphylactic shock
• decreases BP as causes small blood vessels dilate but large to constrict (large not really involved in control BP)

–involved in inflammation - increases vascular permeability by causing arteriolar + venular dilation but veins constrict build hydrostatic pressure fluid forced out exdutive leads to runny nose, watery eyes

Question 14

H2 receptors

Answer 14

stimulates adenyl cyclase activity

-causes stomach release acid (ranitidine used block h2 receptor prevent gastric ulcers)

Question 15

H3 receptor

Answer 15

linked Gi/Go reduces cAMP- reduce neurotransmitter release as open
k+ channel, close ca2+

Question 16

H4 receptor

Answer 16

found in cells of immune system

increases ip3 = increases calcium in cell

Question 17

triple response

Answer 17

mediated by H1

histamine –> acts on H1
flush=arteriolar dilation
flare= dilation of surrounding vessels
wheal= site odema due to capillary + venule dilation

Question 18

uses of h1 antihistamine

Answer 18

• nausea (1st gen)
• sedation (1st gen)
• allergic reaction