Antihistamine Mechanism on Allergic Disease Treatments: Receptor Blockage – Receptor Inactivation
| Main Author: | Pohan, Saut Sahat; Faculty of Medicine Airlangga University/ Dr. Soetomo Hospital, Surabaya |
|---|---|
| Format: | application/pdf eJournal |
| Bahasa: | eng |
| Terbitan: |
Journal of the Indonesian Medical Association
, 2007
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| Online Access: |
http://indonesia.digitaljournals.org/index.php/idnmed/article/view/497 |
Daftar Isi:
- H1 antihistamines are competitive inhibitors to histamine H1 receptor. They bind to the receptor without activating it but prevent the subsequent binding of histamine. However, recent studies have shown that H1 antihistamines are not antagonists but inverse agonists. They have capacity to turn off an active receptor. H1 antihistamines, acting as inverse agonists, have the ability to turn off these receptors and reduce allergic inflammation. Classical models of G-protein-coupled receptors (GPCRs) require the occupation of receptors by an agonist to initiate the activation of signal transduction pathways. Recently, the expression of GPCRs in recombinant systems revealed a constitutive spontaneous receptor activity, which is independent to receptors occupancy by an agonist. An agonist would lead the increase of the basic activity leading to continuous activation signals. Gbg and Gaq/11 sub unit have an important role in sending constitutive signal and agonist-mediated signal. Thus, H1 constitutive receptor has an important role inactivating the constitutive NF-κB. The H1 receptor-mediated NF-κB activation is inhibited byseveral H1 antagonists, such as cetirizine, ebastine, levocetirizine. Histamine molecules exist andtheir reactions take place in three dimensional space. Therefore, they are stereospecific binding between the H1 receptors and the histamine/antihistamine. Several antihistamines such as cetirizine, loratadine, levocetirizine, dextrocetirizine bind perfectly with the H1-receptors in a stereo specific binding, but the binding affinity among the antihistamines is different. Further investigations in knowing how antihistamines work, such as the anti-inflammation mechanisms, the H1 receptor structure and the binding affinity of H1 antihistamines to receptors are needed in finding effective antihistamines to treat allergic diseases.Keywords: H1 receptor , agonist, inverse agonist, NF-κB