thumb | right | The structure of histamine H1 receptor
The histamine receptors are a class of G protein–coupled receptors which bind histamine as their primary endogenous ligand. Histamine is a neurotransmitter involved in various physiological processes. There are four main types of histamine receptors: H1, H2, H3, and H4. H1 receptors are linked to allergic responses, H2 to gastric acid regulation, H3 to neurotransmitter release modulation, and H4 to immune system function.
There are four known histamine receptors:
- H<sub>1</sub> receptorPrimarily located on smooth muscle cells, endothelial cells, and neurons. Activation of H1 receptors mediates various responses, including smooth muscle contraction (leading to bronchoconstriction, intestinal cramping), increased vascular permeability (resulting in edema), and stimulation of sensory nerve endings (causing itching and pain). H1 antagonists, commonly known as antihistamines, are used to alleviate symptoms of allergies and allergic reactions.
- H<sub>2</sub> receptorFound mainly in the stomach lining (parietal cells), H2 receptors regulate gastric acid secretion by stimulating the production of hydrochloric acid. H2 antagonists (H2 blockers) are used to reduce stomach acid production and treat conditions like gastroesophageal reflux disease (GERD) and peptic ulcers.
- H<sub>4</sub> receptorInitially discovered on immune cells, particularly mast cells, eosinophils, and T cells, H4 receptors are involved in immune responses, including chemotaxis (cellular movement in response to chemical signals) and cytokine production. These receptors play a role in inflammation and allergic reactions. Research on H4 receptors is ongoing to better understand their involvement in immune-related disorders and to develop potential therapeutic interventions.
Comparison
{| class="wikitable"
|+Histamine receptors
|-
! Receptor !! Location !! Mechanism of action !! Function !! Antagonists !! Uses of antagonists
|-
! H<sub>1</sub>
| Throughout the body, especially in:
| G<sub>q</sub>
|
- ileum contraction
- modulate circadian cycle
- itching
- systemic vasodilatation (indirect effect throughout the increased production of NO)
- bronchoconstriction (allergy-induced asthma)
|
- H<sub>1</sub>-receptor antagonists
- Diphenhydramine
- Loratadine
- Cetirizine
- Fexofenadine
- Clemastine
- Rupatadine
|
|-
! H<sub>2</sub>
|
| G<sub>s</sub> <br /> ↑ cAMP<sup>2+</sup>
|
- speed up sinus rhythm
- Stimulation of gastric acid secretion
- Smooth muscle relaxation
- Inhibit antibody synthesis, T-cell proliferation and cytokine production
|
- H<sub>2</sub>-receptor antagonists
- Ranitidine
- Cimetidine
- Famotidine
- Nizatidine
|
|-
! H<sub>3</sub>
|
| G<sub>i</sub>
|
- Decrease Acetylcholine, Serotonin and Norepinephrine Neurotransmitter release in CNS
- Presynaptic autoreceptors
|
- H<sub>3</sub>-receptor antagonists
- ABT-239
- Ciproxifan
- Clobenpropit
- Thioperamide
|
|-
! H<sub>4</sub>
|
- Immune system
- lymphocytes
- leukocytes
- Lymphoid organs
- thymus
- spleen
- liver
- gastrointestinal tract (GIT)
- pancreas
- bile ducts
| G<sub>i</sub>
|
- mediate mast cell chemotaxis.
|
- H<sub>4</sub>-receptor antagonists
- Thioperamide
- JNJ 7777120
| , no clinical uses exist.<br />Potential uses include:f
|-
|}
There are several splice variants of H<sub>3</sub> present in various species. Though all of the receptors are 7-transmembrane g protein coupled receptors, H<sub>1</sub> and H<sub>2</sub> are quite different from H<sub>3</sub> and H<sub>4</sub> in their activities. H<sub>1</sub> causes an increase in PIP<sub>2</sub> hydrolysis, H2 stimulates gastric acid secretion, and H3 mediates feedback inhibition of histamine.
References
External links
- Holger Stark: Histamine Receptors, BIOTREND Reviews No. 01, November 2007