Identification of new neuroactive steroids that are able to interact with allosteric binding sites on purinergic P2X receptors
| Autor: | Sivčev, Sonja |
|---|---|
| Přispěvatelé: | Zemková, Hana, Vyklický, Vojtěch, Stojilkovic, Stanko S. |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
ivermectin
alosterické modulátory allosteric modulators neurosteroidy neurosteroids primární buněčná kultura ion channels Purinergic signaling anterior pituitary extracelulární ATP hormone secretion sekrece hormonů extracellular ATP ivermektin purinergní P2X receptory primary cell culture Purinergní signalizace purinergic P2X receptors patch clamp adenohypofýza iontové kanály HEK293 cells HEK293 buňky |
| Popis: | (EN) Purinergic P2X receptors are ATP-gated cation channels with multiple physiological roles and are emerging as important therapeutic targets in a range of diseases. P2X subunit consists of two transmembrane helices (TM1 and TM2), an extracellular ATP-binding domain, and intracellular N- and C- termini. Seven different P2X subunits (P2X1-7) can assemble to form homotrimeric or heterotrimeric ion channels permeable for monovalent cations and calcium. P2X are ubiquitously expressed. Among them, P2X2, P2X4, and P2X7 are the most abundant within the brain. The activity of P2X depends not only on the presence of ATP but also on allosteric modulators that may inhibit or potentiate the activity of these channels. Our aim was to identify new molecules that could interact with allosteric binding sites on P2X receptors, design and synthesize new analogues of neurosteroids, and define crucial receptor domains and amino acids important for neurosteroid binding. By using a patch-clamp electrophysiology technique we recorded ATP-induced currents in HEK293T cells transfected with rat P2X2, P2X4, and P2X7, as well as in the rat anterior pituitary cells and hypothalamic neurons endogenously expressing these receptors. We found that 17β-ester derivatives of testosterone, namely testosterone butyrate and... |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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