Difference Between H1 and H2 Receptors

The key difference between H1 and H2 receptors is that the H1 receptor couples with Gq/11 stimulating phospholipase C while the H2 receptor interacts with Gs to activate adenylyl cyclase.

Histamine is an organic nitrogenous compound that involves local immune responses. Furthermore, it works as a neurotransmitter in the central nervous system and the uterus. It participates in inflammatory responses and works as a mediator of itching. Basophils and mast cells generate histamine, and histamine increases the permeability of capillaries to white blood cells and necessary proteins to work against the infectious agents. In order to execute the effect of histamine, it should be bind to G protein-coupled histamine receptors. There are four types of histamine receptors namely H1, H2, H3, and H4. H1 and H2 are present in associative with the central nervous system and periphery. Hence, the difference between H1 and H2 receptors mainly lies with their mechanism of action.

CONTENTS

1. Overview and Key Difference
2. What are H1 Receptors
3. What are H2 Receptors
4. Similarities Between H1 and H2 Receptors
5. Side by Side Comparison – H1 vs H2 Receptors in Tabular Form
6. Summary

What are H1 Receptors?

Histamine H1 receptor or H1 receptor is one of the four histamine binding receptors, which is a G protein-coupled receptor. This is the main receptor that involves creating symptoms during the allergic reactions. It is a protein as well as a heptahelical transmembrane molecule. Thus, it is able to transduce signals from the external environment to the intracellular second messengers through G protein-coupled reactions.

Moreover, the wide distribution of H1 receptors can be observed at the periphery of the body, especially in the smooth muscles. Apart from the periphery, H1 receptors reside in the adrenal medulla, vascular endothelium, heart and central nervous system, etc. The functions mediated by H1 receptor bindings are a contraction of smooth muscles, an increase in capillary permeability, mediating neurotransmission in the CNS, etc.

What are H2 Receptors?

H2 receptor is another histamine binding receptor, which is a Gs protein-coupled receptor. When this receptor-stimulated, through activation of adenylyl cyclase, it increases the intracellular concentration of cAMP in many tissues. The wide distribution of H2 receptors can be seen in the central nervous system especially in the brain. Receptor concentration is high in the basal ganglia, hippocampus, amygdala and cerebral cortex.

Hypothalamus and cerebellum have a low concentration of H2 receptors. Furthermore, H2 receptors present in the parietal cells located in the stomach. It is responsible for regulating the gastric acid level. And also H2 receptors can be seen in the heart, uterus and vascular smooth muscle cells. When the binding of histamine to H2 receptors blocks, it can reduce the amount of acid produced by the stomach. Hence, H2 receptor agonists are popular H2 blockers which use to treat duodenal ulcers, gastric ulcers, Zollinger -Ellison disease etc.

What are the Similarities Between H1 and H2 Receptors?

• H1 and H2 receptors are G protein-coupled receptors.
• Histamine binds with both these receptors.
• They are proteins.
• Also, both receptors are situated in various parts of the body.
• Mainly, they are widely distributed in the mammalian brain.
• Furthermore, both mediate histamine actions.

What is the Difference Between H1 and H2 Receptors?

H1 and H2 receptors are two types of histamine binding receptors which use to exert the histamine action. The difference between H1 and H2 receptors mainly lies in the mechanism of each receptor. H1 receptors couple with Gq/11 stimulating phospholipase C, while H2 receptors interact with Gs to activate adenylyl cyclase. Another difference between H1 and H2 receptors is that H1 receptors are responsible mainly for the internal clock while H2 receptors are responsible for the regulation of the gastric acid level.

The below infographic shows the difference between H1 and H2 receptors in tabular form.

Summary – H1 vs H2 Receptors

Both H1 and H2 receptors are rhodopsin-like G protein-coupled receptors. They mediate the action of histamine in allergic reactions and many other physiological reactions. Histamine binds to four histamine receptors among them H1 and H2 are present mainly in the central nervous system. Thus, the H1 receptor couples to Gq/11 stimulating phospholipase C, whereas the H2 receptor interacts with Gs to activate adenylyl cyclase. Furthermore, H1 receptor mainly involves in the regulation of the sleep-wake cycle while H2 receptor mainly involves in the stimulation of parietal cells to secrete gastric acid. This is the difference between H1 and H2 receptors.

Reference:

1.“Histamine H2 Receptor.” NeuroImage, Academic Press. Available here  
2.EMBL-EBI, InterPro. “InterPro.” The European Bioinformatics Institute < EMBL-EBI. Available here  

Image Courtesy:

1.”H1 Receptor with Doxepin”By Nakane, Tatsuro Shimamura, Mitsunori Shiroishi, Simone Weyand, Hirokazu Tsujimoto, Graeme Winter, Vsevolod Katritch, Ruben Abagyan, Vadim Cherezov, Wei Liu, Gye Won Han, Takuya Kobayashi, Raymond C. Stevens & So Iwata (July 2011). “Structure of the human histamine H1 receptor complex with doxepin”. Nature 475 (7354): 65–70. DOI:10.1038/nature10236. PMID 21697825., (Public Domain) via Commons Wikimedia  
2.”Determinants of Gastric Acid Secretion”By Adam L. VanWert, Pharm.D., Ph.D. – Own work, (Public Domain) via Commons Wikimedia