Synthetic testosterone derivatives modulate rat P2X2 and P2X4 receptor channel gating

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F19%3A00507827" target="_blank" >RIV/67985823:_____/19:00507827 - isvavai.cz</a>

Alternative codes found

RIV/61388963:_____/19:00507827 RIV/00216208:11310/19:10409237 RIV/00216208:11110/19:10409237

Result on the web

<a href="https://doi.org/10.1111/jnc.14718" target="_blank" >https://doi.org/10.1111/jnc.14718</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/jnc.14718" target="_blank" >10.1111/jnc.14718</a>

Result language

angličtina

Original language name

Synthetic testosterone derivatives modulate rat P2X2 and P2X4 receptor channel gating

Original language description

P2X receptors (P2XRs) are ATP-gated cationic channels that are allosterically modulated by numerous compounds, including steroids and neurosteroids. These compounds may both inhibit and potentiate the activity of P2XRs, but sex steroids such as 17 beta-estradiol or progesterone are reported to be inactive. Here, we tested a hypothesis that testosterone, another sex hormone, modulates activity of P2XRs. We examined actions of native testosterone and a series of testosterone derivatives on the gating of recombinant P2X2R, P2X4R and P2X7R and native channels expressed in pituitary cells and hypothalamic neurons. The 17 beta-ester derivatives of testosterone rapidly and positively modulate the 1 mu M ATP-evoked currents in P2X2R- and P2X4R-expressing cells, but not agonist-evoked currents in P2X7R-expressing cells. In general, most of the tested testosterone derivatives are more potent modulators than endogenous testosterone. The comparison of chemical structures and whole-cell recordings revealed that their interactions with P2XRs depend on the lipophilicity and length of the alkyl chain at position C-17. Pre-treatment with testosterone butyrate or valerate increases the sensitivity of P2X2R and P2X4R to ATP by several fold, reduces the rate of P2X4R desensitization, accelerates resensitization, and enhances ethidium uptake by P2X4R. Native channels are also potentiated by testosterone derivatives, while endogenously expressed GABA receptors type A are inhibited. The effect of ivermectin, a P2X4R-specific allosteric modulator, on deactivation is antagonized by testosterone derivatives in a concentration-dependent manner. Together, our results provide evidence for potentiation of particular subtypes of P2XRs by testosterone derivatives and suggest a potential role of ivermectin binding site for steroid-induced modulation.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Neurochemistry

ISSN

0022-3042

e-ISSN

—

Volume of the periodical

150

Issue of the periodical within the volume

1

Country of publishing house

US - UNITED STATES

Number of pages

16

Pages from-to

28-43

UT code for WoS article

000472767700002

EID of the result in the Scopus database

2-s2.0-85067474971