TRPV1

• OMIM: 602 076
• UniProt: Q8NER1

Transient Receptor Potential Vanilloid 1 ( TRPV1 ), outdated vanilloid receptor 1 (VR1 ) or capsaicin receptor is an ion channel in the sensory neurons of the central and peripheral nervous system of vertebrates that is responsible as a pain receptor for the perception of a number of harmful stimuli. Because of its importance for the development of pain applies TRPV1 as an important object of investigation in the development of new analgesics for humans. Furthermore, the receptor plays a role in the sensation of taste sharpness.

The transport equation is:

General

TRPV1 is a transmembrane protein in the nerve cells of the central and peripheral nervous system that belongs to the family of TRP ion channels. It is believed that TRPV1 mostly as a tetramer of four identical subunits of 839 amino acids in length, respectively in humans occurs in the middle of which a pore is closable. A high-resolution 3D structure of the complete protein is not present in the PDB crystal structure of a small section of the rat protein is only filed. The receptor was described in 1997 for the first time.

Operation

TRPV1 can be activated by a number of, mostly as perceived harmful influences. These include high temperatures in excess of 42 or 43 ° C, and a decreased pH value below 5.9. The receptor is also sensitive to certain activating substances called agonists, as its most famous representative applies the sharpness mediating capsaicin from peppers and chillies.

Upon activation, in the opening of the Rezeptorpore, so that the cell membrane is permeable to calcium ions. Through the consequent depolarization of the cell membrane, an action potential is initiated which propagates through the nerve system and brain leads to the perception of pain.

Development of pain medications

Because of its role in pain perception applies TRPV1 as important starting point in the development of new analgesics. Described in the literature is about the administration of capsaicin at anguished patients. Through constant irritation of the receptor it comes to desensitization and consequently to reduced sensitivity to the TRPV1 -mediated pain stimuli.

Another approach consists in the administration of antagonists. These are substances which prevent the opening of the Rezeptorpore by biospecific interaction with the TRPV1 receptor. Therefore, no more calcium ions from passing through the membrane and the formation of a nociceptive action potential is prevented. The development of new TRPV1 antagonists for use in the treatment of pain was and is the subject of research programs of the pharmaceutical industry. As problematic in the clinical testing of some drug candidates has been found that there has been sporadically threatening rise in body temperature. Furthermore, it is reported by a lower heat sensitivity of the test subjects, which could increase the risk of burns in various situations (eg hand on hot plate).