TRPV1: A Promising drug target for the treatment of various conditions

Abstract

Nobelova nagrada za fiziologiju i medicinu za 2021. dodeljena je naučnicima koji su identifikovali receptore za temperaturu i dodir. Da bi sproveli ovo ispitivanje, istraživači su koristili kapsaicin, jedinjenje koje čili paprici daje toplotu, kako bi otkrili receptore koji omogućavaju ljudima da osete “gorući” ukus čilija. Pokazano je da se transient receptor potential vanilloid 1 (TRPV1), koji predstavlja jonski kanal prisutan na senzornim neuronima, otvara u prisustvu kapsaicina ili toplote, propuštajući naelektrisane jone kalcijuma u ćeliju. Takav priliv kalcijuma pokreće električne signale koji se šalju u mozak da upozore na toplotu. TRPV1 se nalazi u somatosenzornom sistemu i služi kao multimodalni senzor različitih štetnih stimulusa. Brojne farmakološke i genetičke studije su potvrdile TRPV1 kao terapeutsku metu u nekoliko pretkliničkih modela hroničnog bola, uključujući maligni, neuropatski, postoperativni i mišićno-skeletni bol. Pored toga, ekspresija TRPV1 se takođe primećuje na ne-neuronskim lokalizacijama, kao što su epitel bešike i pluća, ćelije kohlee u uhu. Stoga, lekovi koji mogu da modulišu aktivnost kanala TRPV1 mogu biti korisni za lečenje različitih stanja u rasponu od hroničnog bola do gubitka sluha. Iako je utvrđeno da antagonisti TRPV1 mogu predstavljati važan dodatak terapiji bola, njihova klinička upotreba je i dalje ograničena značajnim neželjenim efektima, kao što je hipertermija. U ovom radu ćemo opisati najvažnije uloge TRPV1 u fiziološkim i patofiziološkim procesima i predstaviti najperspektivnije lekove koji deluju preko TRPV1.The 2021. Nobel Prize in Physiology or Medicine was awarded to scientists who have identified receptors for temperature and touch. In order to conduct this examination, researchers used capsaicin, the compound that gives chili peppers their heat, to discover receptor proteins that allow people to feel chili’s burn. It is shown that transient receptor potential vanilloid 1 (TRPV1), which represents an ion channel present on sensory neurons, opens when it encounters capsaicin or heat, allowing charged calcium ions into the cell. That flood of calcium triggers electrical signals that are sent to the brain to warn of heat. TRPV1 is found in the somatosensory system and serves as a multimodal sensor of different noxious stimuli. Numerous pharmacological and genetic studies have validated TRPV1 as a therapeutic target in several preclinical models of chronic pain, including cancer, neuropathic, postoperative and musculoskeletal pain. Additionally, expression of TRPV1 is also observed in non-neuronal sites such as the epithelium of bladder and lungs, cells of the cochlea. Therefore, drugs which could modulate TRPV1 channel activity could be useful for the treatment of conditions ranging from chronic pain to hearing loss. While antagonists of TRPV1 were found to be a valuable addition to therapy of pain, their clinical use has still been limited by significant side effects, such as hyperthermia. In this review, we will describe the most important roles of TRPV1 in physiological and pathophysiological processes and present the most promising TRPV1-targeted drugs