pathological and physiological role of histamine

1. SEMINAR ON HISTAMINE
Under the guidance of Presented by
Prof .Mrs .Santhrani Thakur Deepika Darnasi ,
M.Pharm ,Ph.D l/ ll M. pharmacy,
Dept. of pharmacology

2. CONTENTS
• INTRODUCTION
• TYPES OF AUTOCOIDS
• LOCATION
• SYNTHESIS
• METABOLISM
• HISTAMINIC RECEPTORS
• PATHOLOGICAL AND PHYSIOLOGICAL ROLE
• PHARMACOLOGICAL ACTIONS
• THERAPEUTIC USES

3. INTRODUCTION
HISTAMINE:
 Amine autocoid.
 Autocoid (Greek word)
autos - self
akos - remedy/self healing substances
 Secreted from special cells (endothelial cells or
tissues) & transported through the circulatory
system to act either locally (at the site of
synthesis or release) or on distant target tissues.

4. TYPES OF AUTOCOIDS
• AMINE AUTOCOIDS : Histamine
5-HT
• PEPTIDE AUTOCOIDS : Angiotensin
Plasma Kinnins
Somatostatin
• PHOSPHALIPID DERIVED
AUTOCOIDS : Eicosanoids(leukotrienes,
PG,Thromboxanes)
Platelet activating factor

5. LOCATION
• Uneven distribution throughout the body.
• Mostly within storage granules of mast cells
(inactive complex) & WBC (basophils and
eosinophils).
• Tissues rich -skin, gastric & intestinal mucosa
,Lungs, liver, placenta.
• Occurs in brain ,epidermis, growing region.
• Tissue fluids minor- blood, plasma, body
secretions, venom,pathological fluids.

6. Synthesis
• Beta -imidazolyl ethylamine,derivative of imidazole.•

7. METABOLISM OF HISTAMINE
Histidine
histidine
decarboxylase
Histamine N-methyl transferase N- methyl
histamine
diamine oxidase oxidase
Methyl imidazole acetic acid
Imidazole acetic acid

8. HISTAMINIC RECEPTORS
HISTAMIN
E
RECEPTOR
H1
RECEPTOR
H2
RECEPTOR
H3
RECEPTOR
H4
RECEPTOR
Receptor
type
GPCR GPCR GPCR GPCR
Location Intestinal,
bronchial,
uterine
smooth
muscles,
CNS,
endothelial
cells,
sensory nerve
endings
On parietal
cells of
GIT,
Blood
vessels,
heart,
brain
On brain,
lungs,
spleen,
skin,
gastric
mucosa,
certain
blood
vessels
On thymus
gland,
small
Intestine,
spleen,
colon,
Bone
marrow,
Present on
surace of
basophils

9. Histamine
receptor
H1
receptor
H2
receptor
H3
receptor
H4
receptor
Specific
agonist
2 methyl
histamine,
2 thiazolyl
etylamine,
2 pyridyl
etylamine
Dimaprit
Impromidin
e
4 –methyl
histamine
α-
Methyl
histamine
Imetit
Clozapin
e
Specific
antagonist
Chlorphenir
amine,
Mepyramin
e
Rantidine,
cimetidin
e
Thioperami
de,
Clobenpropi
t
burimamide
thiopera
mide

10. HISTAMINE
RECEPTOR
H1
RECEPTOR
H2
RECEPTOR
H3
RECEPTOR
H4
RECEPTOR
Mechanism
of
action
Hydrolysis of
PIP2
Increases IP3
and DAG
levels
Increase
in CAMP
Levels
Decrease in
CAMP and
calcium
levels
Decrease
in the
levels of
CAMP and
calcium
influx
Release of
intracellular
calcium
levels
Causes
opening of
potassium
channels
Phosporylati
on
of
proteins
Activation of
protein
kinase c

11. PHARMACOLOGICAL ACTIONS OF RECEPTORS
• H1 RECEPTORS
 Contraction of smooth
muscles
 Vasodilation of blood
vessels
 Increase in capillary
permeability
• H3 RECEPTORS
 Vasodilation of blood vessels
 Decreases
neurotransmitter release
• H2 RECEPTORS
 Increases gastric secretion
from gastric glands
 Vasodilation of blood vessels
 Relaxation of uterine smooth
muscles
 Positive inotropic and
chronotropic effects on heart
H4 RECEPTORS
 Causes chemotaxis of WBC

12. PATHOPHYSIOLOGICAL ROLE
PATHOLOGICAL ROLE
• In Hypersensitivity reactions
• In Inflammation
PHYSIOLOGICAL ROLE
• Gastric secretion
• Neuronal Transmission
• Tissue growth and repair

13. IN HYPERSENSITIVITY REACTIONS

14. • HISTAMINE RESPONSIBLE :
o Utricaria (skin rashes)
o angioedema (swelling of tongue ,lips,
eyes)
o Bronchoconstriction
o Anaphylactic shock

15. INFLAMMATION
.Histamine –
mediator of vasodilation and changes that
occur during inflammation.

16. INFLAMMATON PROCESS

17. DIAGRAM OTHER VIEW

18. GASTRIC ACID SECRETION
• DIAGRAM

19. • Secretion of Hcl by gastric parietal cell

21. IN NEURONAL TRANSMISSION

22. TISSUE GROWTH AND REPAIR
• Histamine-tissue amine,as tissues contain high
concentrations of histamine ,plays role in
growth and regeneration of tissues.
• Treats or prevents breast cancer.
• Blood merges with cholesterol and forms DDA
(Dendrogenin A) A compound with anti-tumour
properties

23. PHARMACOLOGICAL ACTIONS
• On blood vessels:
 Dilates of pulmonary vessels,
 Dilates cerebal blood vessels,
 H1-vasodilation-SHORT
 H2-Vasodilation in smooth muscles
( PROLONGED)
Intradermal injection–TRIPLE RESPONSE:
Flush/red reaction , Wheal ,Flare

24. On heart:
 H2-Positive chronotropic and inotropic effect.
 H1-decrease AV conduction
On smooth muscles:
 H1-stimulant effect on smooth muscles.
 contraction of smooth muscles causing
bronchoconstriction and increased motility of
intestinal mucosa.
• On gastric glands:H2
• On CNS
• On ganglionic cells

25. THERAPEUTIC USES
• Diagnostic purposes.
 positive control injection in skin hyper
reactivity testing.
 Test acid secreting capacity of stomach.
 Clinical diagnosis of pheochromocytoma.

26. REFERENCES
• ESSENTIALS OF MEDICAL PHARMACOLOGY,
6th Edition ,K D Tripathi.
• THE PHARMACOLOGICAL BASIS OF
THERAPEUTICS, Goodman and Gilman’s,
12th Edition.
• RANG AND DALE ,www.wikipedia.org

27. THANK
YOU