P2Y11 Purinoceptor Mediates the ATP-Enhanced Chemotactic Response of Rat Neutrophils

ATP and hydrolysis products of ATP like adenosine regulate the chemotaxis of neutrophils by activating purinoceptors and adenosine receptors. The present study was designed to examine exogenous ATP, activation of purinoceptors, and activation of A3 adenosine receptor as key steps in the signal casca...

Full description

Bibliographic Details
Main Authors: Feras Alkayed, Masanori Kashimata, Noriko Koyama, Toru Hayashi, Yasuo Tamura, Yukio Azuma
Format: Article
Language:English
Published: Elsevier 2012-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319304177
_version_ 1819079916743819264
author Feras Alkayed
Masanori Kashimata
Noriko Koyama
Toru Hayashi
Yasuo Tamura
Yukio Azuma
author_facet Feras Alkayed
Masanori Kashimata
Noriko Koyama
Toru Hayashi
Yasuo Tamura
Yukio Azuma
author_sort Feras Alkayed
collection DOAJ
description ATP and hydrolysis products of ATP like adenosine regulate the chemotaxis of neutrophils by activating purinoceptors and adenosine receptors. The present study was designed to examine exogenous ATP, activation of purinoceptors, and activation of A3 adenosine receptor as key steps in the signal cascades that control cell orientation and migration of rat neutrophils. One or more of those steps might be potential therapeutic targets for treatment of inflammatory diseases. The chemotaxis of rat neutrophils was stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) and measured with an EZ-TAXIScan apparatus. The effects of apyrase, exogenous ATP, suramin (P2X and P2Y blocker), PPADS (a P2X blocker), TNP-ATP (P2X1 and P2X3 antagonist), and Reactive Blue 2 (a P2Y blocker) on the chemotactic response were also investigated. Rat neutrophil chemotaxis was significantly suppressed by apyrase. fMLP induced rat neutrophil chemotaxis was potentiated by ATP, blocked by suramin, not affected by PPADS or TNP-ATP, and significantly inhibited by RB-2. Western blotting showed that A3, P2Y2, and P2Y11 were expressed in rat neutrophils. The chemotactic response of rat neutrophils to fMLP stimulation is potentiated by ATP via P2Y11 purinoceptors but not P2X purinoceptors or A3 adenosine receptor, and that the response plays a critical role in host defense and pathogenicity.[Supplementary Movies: available only at http://dx.doi.org/10.1254/jphs.12173FP] Keywords:: chemotaxis, extracellular nucleotide, EZ-TAXIScan, neutrophil, purinoceptor
first_indexed 2024-12-21T19:36:36Z
format Article
id doaj.art-6883633440984bafbe47191b6cc93654
institution Directory Open Access Journal
issn 1347-8613
language English
last_indexed 2024-12-21T19:36:36Z
publishDate 2012-01-01
publisher Elsevier
record_format Article
series Journal of Pharmacological Sciences
spelling doaj.art-6883633440984bafbe47191b6cc936542022-12-21T18:52:36ZengElsevierJournal of Pharmacological Sciences1347-86132012-01-011204288295P2Y11 Purinoceptor Mediates the ATP-Enhanced Chemotactic Response of Rat NeutrophilsFeras Alkayed0Masanori Kashimata1Noriko Koyama2Toru Hayashi3Yasuo Tamura4Yukio Azuma5Department of Dental Pharmacology, 1851-1 Hozumi, Mizuho-City, Gifu 501-0296, JapanDepartment of Dental Pharmacology, 1851-1 Hozumi, Mizuho-City, Gifu 501-0296, JapanDepartment of Dental Pharmacology, 1851-1 Hozumi, Mizuho-City, Gifu 501-0296, JapanDepartment of Dental Pharmacology, 1851-1 Hozumi, Mizuho-City, Gifu 501-0296, JapanDepartment of Pediatric Dentistry, Asahi University School of Dentistry, 1851-1 Hozumi, Mizuho-City, Gifu 501-0296, JapanDepartment of Dental Pharmacology, 1851-1 Hozumi, Mizuho-City, Gifu 501-0296, Japan; Corresponding author. azuma@dent.asahi-u.ac.jpATP and hydrolysis products of ATP like adenosine regulate the chemotaxis of neutrophils by activating purinoceptors and adenosine receptors. The present study was designed to examine exogenous ATP, activation of purinoceptors, and activation of A3 adenosine receptor as key steps in the signal cascades that control cell orientation and migration of rat neutrophils. One or more of those steps might be potential therapeutic targets for treatment of inflammatory diseases. The chemotaxis of rat neutrophils was stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) and measured with an EZ-TAXIScan apparatus. The effects of apyrase, exogenous ATP, suramin (P2X and P2Y blocker), PPADS (a P2X blocker), TNP-ATP (P2X1 and P2X3 antagonist), and Reactive Blue 2 (a P2Y blocker) on the chemotactic response were also investigated. Rat neutrophil chemotaxis was significantly suppressed by apyrase. fMLP induced rat neutrophil chemotaxis was potentiated by ATP, blocked by suramin, not affected by PPADS or TNP-ATP, and significantly inhibited by RB-2. Western blotting showed that A3, P2Y2, and P2Y11 were expressed in rat neutrophils. The chemotactic response of rat neutrophils to fMLP stimulation is potentiated by ATP via P2Y11 purinoceptors but not P2X purinoceptors or A3 adenosine receptor, and that the response plays a critical role in host defense and pathogenicity.[Supplementary Movies: available only at http://dx.doi.org/10.1254/jphs.12173FP] Keywords:: chemotaxis, extracellular nucleotide, EZ-TAXIScan, neutrophil, purinoceptorhttp://www.sciencedirect.com/science/article/pii/S1347861319304177
spellingShingle Feras Alkayed
Masanori Kashimata
Noriko Koyama
Toru Hayashi
Yasuo Tamura
Yukio Azuma
P2Y11 Purinoceptor Mediates the ATP-Enhanced Chemotactic Response of Rat Neutrophils
Journal of Pharmacological Sciences
title P2Y11 Purinoceptor Mediates the ATP-Enhanced Chemotactic Response of Rat Neutrophils
title_full P2Y11 Purinoceptor Mediates the ATP-Enhanced Chemotactic Response of Rat Neutrophils
title_fullStr P2Y11 Purinoceptor Mediates the ATP-Enhanced Chemotactic Response of Rat Neutrophils
title_full_unstemmed P2Y11 Purinoceptor Mediates the ATP-Enhanced Chemotactic Response of Rat Neutrophils
title_short P2Y11 Purinoceptor Mediates the ATP-Enhanced Chemotactic Response of Rat Neutrophils
title_sort p2y11 purinoceptor mediates the atp enhanced chemotactic response of rat neutrophils
url http://www.sciencedirect.com/science/article/pii/S1347861319304177
work_keys_str_mv AT ferasalkayed p2y11purinoceptormediatestheatpenhancedchemotacticresponseofratneutrophils
AT masanorikashimata p2y11purinoceptormediatestheatpenhancedchemotacticresponseofratneutrophils
AT norikokoyama p2y11purinoceptormediatestheatpenhancedchemotacticresponseofratneutrophils
AT toruhayashi p2y11purinoceptormediatestheatpenhancedchemotacticresponseofratneutrophils
AT yasuotamura p2y11purinoceptormediatestheatpenhancedchemotacticresponseofratneutrophils
AT yukioazuma p2y11purinoceptormediatestheatpenhancedchemotacticresponseofratneutrophils