This document discusses histamine receptors and histamine intolerance. It describes the four types of histamine receptors (H1-H4), their locations in the body, and their downstream mechanisms of action. H1 receptors act through the IP3-DAG pathway while H2 receptors act through the cAMP pathway. The document also summarizes what causes high histamine levels and symptoms of histamine intolerance such as headaches and digestive issues. Treatments include avoiding histamine-rich foods, increasing histamine-processing enzymes, and using antihistamines.

1. HISTAMINE RECEPTORS
&
HISTAMINE INTOLERANCE
By
MARYAM NASIR
18551507-083
TO
DR.M.GHULAM MUSTAFA
1

2. CONTENTS
Histamine Receptors
1. H1 Histamine Receptors
2. H2 Histamine Receptors
 Mechanism of Action
o H1 Histamine Receptors: IP3 DAG Pathway
o H2 Histamine Receptors: cAMP Pathway
Histamine Intolerance
o What causes high histamine levels?
o Histamine intolerance symptoms
o Histamine intolerance treatment
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3. HISTAMINE RECEPTORS
 When histamine released, it can bind to
histamine receptors found throughout the
body.
 When histamine binds to histamine receptors,
various effects are possible and dependent on
tissue type.
HISTAMINE RECEPTORS
H1 H2 H3 H4
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Wilson and Gisvold’s Textbook of ORGANIC MEDICINAL AND PHARMACEUTICAL CHEMISTRY (12th edition)
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4. Receptor subtype Receptor proteins Distribution Post receptor
Mechanism
H1 Receptor 487 amino acids Smooth muscle,
endothelium, brain
Gq, ↑ IP3, DAG
H2 Receptor 359 amino acids Gastric mucosa, cardiac
muscle, mast cells, brain
Gs, ↑ cAMP
H3 Receptor 445 amino acids brain, myenteric plexus,
other neurons
Gi, ↓ cAMP
H4 Receptor 390 amino acids Eosinophils, neutrophils,
CD4 T cells
Gi, ↓ cAMP
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HISTAMINE RECEPTOR SUBTYPES
Bertram G. Katzung, Basic and Clinical pharmacology (12th edition)
MARYAM NASIR
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5. 5

6. H1 RECEPTOR BINDING
 Location
o Smooth muscle, Endothelium, CNS tissue
 Action
o Dilatation of small blood vessels flushing and hypotension
o Increase capillary permeability Edema
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Pharmacology (Lippincott lllustraded Reviews Series) 7th Edition
MARYAM NASIR
18551507-083

7. H1 RECEPTOR BINDING
 Peripheral sensory neurons
Causes itching and sometimes pain
 Intestinal smooth muscle
Causes constriction, cramps and may be diarrhea
 Pulmonary smooth muscle
Causes constriction of bronchioles leading to decreased lung capacity and asthma
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Pharmacology (Lippincott lllustraded Reviews Series) 7th Edition
MARYAM NASIR
18551507-083

8. H1 AND H2 RECEPTOR BINDING
 Cardiovascular Effects
Drops BP by inducing vasodilatation of
arterioles and pre capillary sphincters
which decreases peripheral resistance.
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Pharmacology (Lippincott lllustraded Reviews Series) 7th Edition
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18551507-083

9. CONT....
 Dermatologist Effects
Dilation and increased permeability of the capillaries results in leakage of proteins
fluid into the tissues.
Which results in ‘Triple response’ seen on the skin
o Reddening of skin due to vasodilatation
o Wheal formation due to increase permeability
o Irregular ‘halo’ flare due to axon reflux
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Pharmacology (Lippincott lllustraded Reviews Series) 7th Edition
MARYAM NASIR
18551507-083

10. H2 RECEPTOR BINDING
 Located on parietal cells
Gastric Effects
 Stimulate gastric acid secretion
by activation of H2 receptors
located on gastric parietal cells in
the lining of stomach
 Parietal cells secrete HCI
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Pharmacology (Lippincott lllustraded Reviews Series) 7th Edition
MARYAM NASIR
18551507-083

11. MECHANISM OF ACTION
 All histamine receptors are G-Protein coupled receptors GPCR belongs to the largest
family of cell surface receptors, and give their action by the mechanism of GPCR.
 They found in Eukaryotic cells
 GPCR also known as 7-transmembrane receptors that sense molecules outside the cell
and activate inside signal transduction pathways and ultimately, cellular responses.
 They are called 7-transmembrane receptors because they pass through the cell
membrane seven time
 Now a days, 30 to 50% drugs target are GPCR
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Bertram G. Katzung, Basic and Clinical pharmacology (12th edition)
MARYAM NASIR
18551507-083

12. GPCR STRUCTURE
Schneider, J. & Carloni, P. (2018). Predicting ligand binding poses for low-resolution membrane protein models: Perspectives from multiscale
simulations. Biochemical and biophysical research communications, 498(2), 366-374.
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13. CONTI....
G Protein Mediated Pathways are:
1. Adenylyl cyclase: cAMP Pathway
2. Phospholipase C: IP3-DAG Pathway
3. Channel regulation
Here;
 H1 receptor are linked to Gq protien and stimulate Phospholipase C: IP3-DAG Pathway
 H2 receptor are linked to Gs protein and stimulate Adenylyl cyclase cAMP Pathway
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Bertram G. Katzung, Basic and Clinical pharmacology (12th edition)
MARYAM NASIR
18551507-083

14. 14

15. HOW NO DROP BLOOD PRESSURE
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NO+ Guanlyl cyclase
GTP cGMP
Myosin light
chain
Smooth
muscle
relaxation
Calmodulin
Activated by ca+2
NO Synthase
(inactive)
NO Synthase
(active)
Arginine NO
Dephosphorylation of
myosin light chain by
Phosphatase enzyme
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16. 16

17. 17

18. HISTAMINE INTOLERANCE
Histamine intolerance occurs when there is a build-up of histamine in the body.
 Histamine intolerance results from a disequilibrium of accumulated histamine and the
capacity for histamine degradation.
 Histamine is a chemical responsible for a few major functions:
o communicates messages to brain
o triggers release of stomach acid to help digestion
o releases after injury or allergic reaction as part of immune response
 When histamine levels get too high or when it can’t break down properly, it can affect normal
bodily functions.
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Maintz, L., & Novak, N. (2007). Histamine and histamine intolerance. The American journal of clinical nutrition, 85(5), 1185-1196.
MARYAM NASIR
18551507-083

19. WHAT CAUSES HIGH HISTAMINE LEVELS?
 You naturally produce histamine along with the enzyme Diamine Oxidase (DAO). DAO is responsible for breaking
down histamine that you take in from foods.
 If you develop a DAO deficiency and are unable to break down histamine, you could develop an intolerance.
Some reasons your DAO enzyme levels could be affected include:
o medications that block DAO functions or prevent production
o histamine-rich foods that cause DAO enzymes to function improperly
o foods that block DAO enzymes or trigger histamine release
 Bacterial overgrowth is another contributing factor for developing a histamine intolerance. Bacteria grows when
food isn’t digested properly, causing histamine overproduction. Normal levels of DAO enzymes can’t break down
the increased levels of histamine in your body, causing a reaction.
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Maintz, L., & Novak, N. (2007). Histamine and histamine intolerance. The American journal of clinical nutrition, 85(5), 1185-1196.
MARYAM NASIR
18551507-083

20. HISTAMINE INTOLERANCE SYMPTOMS
Histamine is associated with common allergic responses and symptoms. Many of
these are similar to those from a histamine intolerance e symptoms
While they may vary, some common reactions associated with this intolerance include:
 headaches or migraines
 nasal congestion or sinus issues
 fatigue
 Hives
In more severe cases of histamine intolerance, you may experience:
 irregular heart rate
 anxiety
 difficulty regulating body temperature
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 digestive issues
 nausea
 vomiting
 abdominal cramping
 tissue swelling
 high blood pressure
 dizziness
Maintz, L., & Novak, N. (2007). Histamine and histamine intolerance. The American journal of clinical nutrition, 85(5), 1185-1196.
MARYAM NASIR
18551507-083

21. HISTAMINE INTOLERANCE TREATMENT
 The best histamine intolerance treatment is avoiding foods that contain or encourage high
levels of the chemical. Your doctor may also recommend using certain supplements to
increase histamine-processing enzymes or antihistamines to ease symptoms.
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https://sa1s3.patientpop.com/assets/docs/170871.pdf
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18551507-083

22. CONTI….
 Diet
Avoid histamine rich food
 Sleep
7-8 hours a night helps everything!
 Support
Health issues and dietary restrictions are stressful and challenging. Seek out support from family, community, faith
organizations, online support groups, local support groups. Avoid those who provide negative interactions. Negative
interactions delay healing.
 Exercise
Any exercise is helpful. Aim for 30-60 minutes daily. Don’t feel bad if you only fit in 15 – it still helps!
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https://www.verywellhealth.com/histamine-intolerance-1324016#toc-treatment
MARYAM NASIR
18551507-083

23. CONTI…..
 Relaxation
The benefits of relaxation techniques cannot be emphasized enough. Breathing exercises or progressive muscle
relaxation are easy, portable, and free. Yoga and meditation are great as well. Relaxation for you may also be
reading, enjoying time with friends, or playing music.
 Medications
Antihistamines, topical steroids/creams, oral steroids, topical homeopathic or plant-based creams, and lotions for
rashes.
 Supplements
There is little to no data on these, but the following are sometimes used. Vit C, B6, Zn, Cu, Magnesium,
Mangosteen, Quercetin, DAO promoters and supplements, topical creams. Please use any supplement under the
guidance of a practitioner. Supplements can have toxic side effects.
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Schnedl, W. J., & Enko, D. (2021). Histamine intolerance originates in the gut. Nutrients, 13(4), 1262.
MARYAM NASIR
18551507-083

24. REFERENCES
 Wilson and Gisvold’s Textbook of ORGANIC MEDICINAL AND PHARMACEUTICAL
CHEMISTRY (12th edition)
 Pharmacology (Lippincott lllustraded Reviews Series) 7th Edition
 Bertram G. Katzung, Basic and Clinical pharmacology (12th edition)
 Maintz, L., & Novak, N. (2007). Histamine and histamine intolerance. The American journal of
clinical nutrition, 85(5), 1185-1196.
 Schnedl, W. J., & Enko, D. (2021). Histamine intolerance originates in the gut. Nutrients, 13(4), 1262.
 https://sa1s3.patientpop.com/assets/docs/170871.pdf
 https://www.verywellhealth.com/histamine-intolerance-1324016#toc-treatment
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