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Transient receptor potential vanilloid (TRPV) channels are a group of six non-selective cation channels (TRPV1–TRPV6) that function as versatile cellular sensors for various physical and chemical stimuli [PMID: 25323745]. These channels are primarily known for their roles in nociception and thermosensation, with TRPV1–TRPV4 acting as thermo-TRPs that respond to different temperature ranges [PMID: 30103444]. TRPV5 and TRPV6 are distinct as they are highly selective for calcium and are crucial for systemic calcium homeostasis in the kidneys and intestines [UniProt: Q9NQA5]. In disease, TRPV channels are heavily implicated in chronic pain, inflammation, and respiratory disorders, making them significant therapeutic targets [PMID: 28244311]. Pharmacological modulation involves both agonists, which can cause desensitization of sensory neurons (e.g., capsaicin), and antagonists designed to block pain signaling [PMID: 23406572]. However, clinical progress for some TRPV1 antagonists has been hindered by side effects such as hyperthermia and impaired heat perception [PMID: 18384730].
Agonism leading to receptor desensitization and Antagonism of channel activation
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