Sandbox Reserved 1652: Difference between revisions
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The state of the channel is modulated by two types of molecules: agents that promote its opening of the channel, called [https://en.wikipedia.org/wiki/Agonist agonists], and agents that induce its closure or prevent its opening, called [https://en.wikipedia.org/wiki/Antagonist antagonists]. | The state of the channel is modulated by two types of molecules: agents that promote its opening of the channel, called [https://en.wikipedia.org/wiki/Agonist agonists], and agents that induce its closure or prevent its opening, called [https://en.wikipedia.org/wiki/Antagonist antagonists]. | ||
=== | == Activators == | ||
===Capsaicin=== | |||
[[Image : https://commons.wikimedia.org/wiki/File:Capsaicin_Formulae.png?uselang=fr]] | [[Image : https://commons.wikimedia.org/wiki/File:Capsaicin_Formulae.png?uselang=fr]] | ||
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This leads to the massive enter of Ca2+ and Na+ in the cytoplasm of the nerve fiber and to the depolarization of the nerve fiber. When depolarization reach a theshold value it triggers the generation of an [https://en.wikipedia.org/wiki/Action_potential action potential] causing a painful sensation.<ref>« TRPV1 », Wikipédia. sept. 09, 2020, Consulté le: déc. 28, 2020. [En ligne]. Disponible sur: https://fr.wikipedia.org/w/index.php?title=TRPV1&oldid=174570512</ref> | This leads to the massive enter of Ca2+ and Na+ in the cytoplasm of the nerve fiber and to the depolarization of the nerve fiber. When depolarization reach a theshold value it triggers the generation of an [https://en.wikipedia.org/wiki/Action_potential action potential] causing a painful sensation.<ref>« TRPV1 », Wikipédia. sept. 09, 2020, Consulté le: déc. 28, 2020. [En ligne]. Disponible sur: https://fr.wikipedia.org/w/index.php?title=TRPV1&oldid=174570512</ref> | ||
===Résinifératoxine (RTX)=== | |||
[[Image : https://upload.wikimedia.org/wikipedia/commons/c/c5/Resiniferatoxin.svg]] | [[Image : https://upload.wikimedia.org/wikipedia/commons/c/c5/Resiniferatoxin.svg]] | ||
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The aromatic is located deeper in the sub-pocket near Y511 and is oriented almost parallel to the aromatic side chain of Y511, so it establishes a strong interaction π-π. The aromatic hydroxyl and methoxy groups of the RTX form strong hydrogen bonds with E570, R557 and S512. The ester group is linked to Y511 and T550 by hydrogen bonds.<ref>K. Elokely et al., « Understanding TRPV1 activation by ligands: Insights from the binding modes of capsaicin and resiniferatoxin », Proc. Natl. Acad. Sci., vol. 113, no 2, p. E137‑E145, janv. 2016, doi:10.1073/pnas.1517288113.</ref> | The aromatic is located deeper in the sub-pocket near Y511 and is oriented almost parallel to the aromatic side chain of Y511, so it establishes a strong interaction π-π. The aromatic hydroxyl and methoxy groups of the RTX form strong hydrogen bonds with E570, R557 and S512. The ester group is linked to Y511 and T550 by hydrogen bonds.<ref>K. Elokely et al., « Understanding TRPV1 activation by ligands: Insights from the binding modes of capsaicin and resiniferatoxin », Proc. Natl. Acad. Sci., vol. 113, no 2, p. E137‑E145, janv. 2016, doi:10.1073/pnas.1517288113.</ref> | ||
=== | == Regulation == | ||
===Sensitization=== | |||
'''Phosphorylation''' of the TRPV1 receptor leads to its sensitization. | '''Phosphorylation''' of the TRPV1 receptor leads to its sensitization. | ||
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As a result phosphorylated TRPV1 are more responsive to agonist because they are overexpressed and the same quantity of agonist leads to a better openings of ion channels. | As a result phosphorylated TRPV1 are more responsive to agonist because they are overexpressed and the same quantity of agonist leads to a better openings of ion channels. | ||
===Desensitization=== | |||
A repeated exposure of TRPV1 to capsaicin fails to activate the receptor. It occurs by a CA2+-dependent mechanism that leads to a '''desphosphorylation''' by the calcineurin [https://en.wikipedia.org/wiki/Phosphatase phosphatase] of the serine and threonine residues which have been previously phosphorylated by PKA. Thus, the decrease in TRPV1 phosphorylation diminish the sensitivity of the capsaicin channel and so a decrease in the response of the capsaicin by '''negative feedback'''. | A repeated exposure of TRPV1 to capsaicin fails to activate the receptor. It occurs by a CA2+-dependent mechanism that leads to a '''desphosphorylation''' by the calcineurin [https://en.wikipedia.org/wiki/Phosphatase phosphatase] of the serine and threonine residues which have been previously phosphorylated by PKA. Thus, the decrease in TRPV1 phosphorylation diminish the sensitivity of the capsaicin channel and so a decrease in the response of the capsaicin by '''negative feedback'''. | ||
