European Journal of Pharmacology, volume 880, pages 173182

Calcium signaling mediated by aminergic GPCRs is impaired by the PI3K inhibitor LY294002 and its analog LY303511 in a PI3K-independent manner

Kotova Polina D ¹

Kochkina Ekaterina N ¹

Lyamin Oleg O ¹

Rogachevskaja Olga A ¹

Korolenko Nina P ¹

Ivashin Denis S ¹

Bystrova Marina F. ¹

Enukashvily N. I. ²

Kolesnikov Stanislav S ¹

Hide authors affiliations Show authors affiliations: 2 affiliations

Institute of Cell Biophysics, Russian Academy of Sciences, Institutional Street 3, Pushchino, Moscow Region, 142290, Russia. |

Institute of Cytology, Russian Academy of Sciences, Tikhoretskii pr 4, St. Petersburg 194064, Russia. |

Publication type: Journal Article

Publication date: 2020-08-01

Elsevier

Journal: European Journal of Pharmacology

Quartile SCImago

Quartile WOS

Impact factor: 5

ISSN: 00142999, 18790712

DOI: 10.1016/j.ejphar.2020.173182

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Pharmacology

Abstract

The phosphoinositide 3-kinase (PI3K) inhibitor LY294002 (LY294) and its much less active analog LY303511 (LY303) constitute the paired probe that is commonly used to demonstrate the involvement of PI3K in intracellular signaling. We studied effects of LY294 and LY303 on Ca2+ signaling initiated by certain GPCR agonists in cells of several lines, including CHO cells expressing the recombinant serotonin receptor 5-HT2C and mesenchymal stromal cells derived from the human adipose tissue (AD-MSCs) and umbilical cord (UD-MSCs). The LY294/LY303 pair exerted apparently specific effects on responsiveness of AD-MSCs to ATP, suggesting the involvement of PI3K in ATP transduction. Surprisingly, LY303 inhibited Ca2+ transients elicited by histamine in the same cells, while LY294 was ineffective. This observation and other findings implicated a PI3K-unrelated mechanism in mediating effects of the LY compound on AD-MSC responsiveness to histamine. With LY303 in the bath, the dose dependence of histamine responses was shifted positively at the invariable number of responsive cells, as would be the case with a competitive antagonist of histamine receptors. Moreover, LY303 and LY294 inhibited Ca2+ transients elicited by acetylcholine and serotonin in UD-MSCs and CHO/5-HT2C cells, respectively. Our overall results argued for the possibility that LY294 and LY303 could directly affect activity of aminergic GPCRs. Thus, LY303511 and LY294002 should be used cautiously in studies of PI3K as a factor of GPCR signaling.

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Stem Cells and Development	Stem Cells and Development, 1, 12.5% Stem Cells and Development 1 publication, 12.5%
NeuroReport	NeuroReport, 1, 12.5% NeuroReport 1 publication, 12.5%
Cells	Cells, 1, 12.5% Cells 1 publication, 12.5%
BBA Advances	BBA Advances, 1, 12.5% BBA Advances 1 publication, 12.5%
Food Science and Nutrition	Food Science and Nutrition, 1, 12.5% Food Science and Nutrition 1 publication, 12.5%
Reproduction, Fertility and Development	Reproduction, Fertility and Development, 1, 12.5% Reproduction, Fertility and Development 1 publication, 12.5%
Cellular Signalling	Cellular Signalling, 1, 12.5% Cellular Signalling 1 publication, 12.5%
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Citations by publishers

	1 2
Elsevier	Elsevier, 2, 25% Elsevier 2 publications, 25%
Mary Ann Liebert	Mary Ann Liebert, 1, 12.5% Mary Ann Liebert 1 publication, 12.5%
Wolters Kluwer Health	Wolters Kluwer Health, 1, 12.5% Wolters Kluwer Health 1 publication, 12.5%
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 1, 12.5% Multidisciplinary Digital Publishing Institute (MDPI) 1 publication, 12.5%
Wiley	Wiley, 1, 12.5% Wiley 1 publication, 12.5%
CSIRO Publishing	CSIRO Publishing, 1, 12.5% CSIRO Publishing 1 publication, 12.5%
	1 2

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Kotova P. D. et al. Calcium signaling mediated by aminergic GPCRs is impaired by the PI3K inhibitor LY294002 and its analog LY303511 in a PI3K-independent manner // European Journal of Pharmacology. 2020. Vol. 880. p. 173182.

GOST all authors (up to 50) Copy

Kotova P. D., Kochkina E. N., Lyamin O. O., Rogachevskaja O. A., Korolenko N. P., Ivashin D. S., Bystrova M. F., Enukashvily N. I., Kolesnikov S. S. Calcium signaling mediated by aminergic GPCRs is impaired by the PI3K inhibitor LY294002 and its analog LY303511 in a PI3K-independent manner // European Journal of Pharmacology. 2020. Vol. 880. p. 173182.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1016/j.ejphar.2020.173182

UR - https://doi.org/10.1016%2Fj.ejphar.2020.173182

TI - Calcium signaling mediated by aminergic GPCRs is impaired by the PI3K inhibitor LY294002 and its analog LY303511 in a PI3K-independent manner

T2 - European Journal of Pharmacology

AU - Kotova, Polina D

AU - Kochkina, Ekaterina N

AU - Lyamin, Oleg O

AU - Rogachevskaja, Olga A

AU - Korolenko, Nina P

AU - Ivashin, Denis S

AU - Bystrova, Marina F.

AU - Enukashvily, N. I.

AU - Kolesnikov, Stanislav S

PY - 2020

DA - 2020/08/01 00:00:00

PB - Elsevier

SP - 173182

VL - 880

SN - 0014-2999

SN - 1879-0712

ER -

BibTex

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BibTex Copy

@article{2020_Kotova,

author = {Polina D Kotova and Ekaterina N Kochkina and Oleg O Lyamin and Olga A Rogachevskaja and Nina P Korolenko and Denis S Ivashin and Marina F. Bystrova and N. I. Enukashvily and Stanislav S Kolesnikov},

title = {Calcium signaling mediated by aminergic GPCRs is impaired by the PI3K inhibitor LY294002 and its analog LY303511 in a PI3K-independent manner},

journal = {European Journal of Pharmacology},

year = {2020},

volume = {880},

publisher = {Elsevier},

month = {aug},

url = {https://doi.org/10.1016%2Fj.ejphar.2020.173182},

pages = {173182},

doi = {10.1016/j.ejphar.2020.173182}

}

Found error?

Publisher

Elsevier

Journal

European Journal of Pharmacology

Quartile SCImago

Quartile WOS

Impact factor

ISSN

00142999 (Print)
18790712 (Electronic)

Labs

Laboratory of Molecular Cell Physiology

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