A novel gliotic P2 receptor mediating cyclooxygenase-2 induction in rat and human astrocytes

Roberta Brambilla, Stefania Ceruti, Walter Malorni, Flaminio Cattabeni, Maria P. Abbracchio

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

In astrocytic cultures maintained in vitro, a brief challenge with the ATP analog α,βmethyleneATP (α,βmeATP) results, 3 days later, in marked elongation of astrocytic processes, an event that resembles the astrocytic hypertrophy known to occur in vivo during reactive astrogliosis. α,βmeATP- induced effects were observed in primary astrocytes obtained from both rat striatum and cortex (a brain area highly involved in chronic neurodegenerative pathologies), as well as in human astrocytoma cells (ADF cells). Purine-induced gliosis could be reversed by the non-selective P2X/P2Y receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), but not by oxidized ATP (an antagonist of the P2X7 receptor), in line with previous studies of our laboratory suggesting the involvement of a P2Y receptor subtype. Induction of reactive gliosis was preceded by increased expression of cyclooxygenase-2 (COX-2), an enzyme whose excessive activation has been implicated in both acute and chronic neurodegenerative diseases. The selective COX-2 inhibitor NS-398 prevented both purine-induced astrogliosis and the associated COX-2 induction, suggesting that inhibition of the transcription of the COX-2 gene may also contribute to the anti-inflammatory properties of this agent. Significant blockade of both α,βmeATP-mediated reactive gliosis and COX-2 induction was also observed with PPADS. These data suggest that COX-2 mediates P2Y receptor-induced reactive astrogliosis, and that antagonists selective for this receptor subtype may represent a novel class of anti-inflammatory agents of potential interest in acute and chronic neurological disorders characterized by an inflammatory component and reactive gliosis. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)3-9
Number of pages7
JournalJournal of the Autonomic Nervous System
Volume81
Issue number1-3
DOIs
StatePublished - Jul 3 2000
Externally publishedYes

Fingerprint

Cyclooxygenase 2
Gliosis
Astrocytes
Anti-Inflammatory Agents
Purinergic P2X7 Receptors
Acids
Cyclooxygenase 2 Inhibitors
Astrocytoma
Nervous System Diseases
Neurodegenerative Diseases
Hypertrophy
Chronic Disease
Adenosine Triphosphate
Pathology
Brain
Enzymes
Genes
purine

Keywords

  • Cyclooxygenase-2
  • Neurodegeneration
  • P2 receptors
  • Reactive astrogliosis

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Neuroscience(all)

Cite this

A novel gliotic P2 receptor mediating cyclooxygenase-2 induction in rat and human astrocytes. / Brambilla, Roberta; Ceruti, Stefania; Malorni, Walter; Cattabeni, Flaminio; Abbracchio, Maria P.

In: Journal of the Autonomic Nervous System, Vol. 81, No. 1-3, 03.07.2000, p. 3-9.

Research output: Contribution to journalArticle

Brambilla, Roberta ; Ceruti, Stefania ; Malorni, Walter ; Cattabeni, Flaminio ; Abbracchio, Maria P. / A novel gliotic P2 receptor mediating cyclooxygenase-2 induction in rat and human astrocytes. In: Journal of the Autonomic Nervous System. 2000 ; Vol. 81, No. 1-3. pp. 3-9.
@article{eefb51aec47a4b3ba42a80acd7dee628,
title = "A novel gliotic P2 receptor mediating cyclooxygenase-2 induction in rat and human astrocytes",
abstract = "In astrocytic cultures maintained in vitro, a brief challenge with the ATP analog α,βmethyleneATP (α,βmeATP) results, 3 days later, in marked elongation of astrocytic processes, an event that resembles the astrocytic hypertrophy known to occur in vivo during reactive astrogliosis. α,βmeATP- induced effects were observed in primary astrocytes obtained from both rat striatum and cortex (a brain area highly involved in chronic neurodegenerative pathologies), as well as in human astrocytoma cells (ADF cells). Purine-induced gliosis could be reversed by the non-selective P2X/P2Y receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), but not by oxidized ATP (an antagonist of the P2X7 receptor), in line with previous studies of our laboratory suggesting the involvement of a P2Y receptor subtype. Induction of reactive gliosis was preceded by increased expression of cyclooxygenase-2 (COX-2), an enzyme whose excessive activation has been implicated in both acute and chronic neurodegenerative diseases. The selective COX-2 inhibitor NS-398 prevented both purine-induced astrogliosis and the associated COX-2 induction, suggesting that inhibition of the transcription of the COX-2 gene may also contribute to the anti-inflammatory properties of this agent. Significant blockade of both α,βmeATP-mediated reactive gliosis and COX-2 induction was also observed with PPADS. These data suggest that COX-2 mediates P2Y receptor-induced reactive astrogliosis, and that antagonists selective for this receptor subtype may represent a novel class of anti-inflammatory agents of potential interest in acute and chronic neurological disorders characterized by an inflammatory component and reactive gliosis. (C) 2000 Elsevier Science B.V.",
keywords = "Cyclooxygenase-2, Neurodegeneration, P2 receptors, Reactive astrogliosis",
author = "Roberta Brambilla and Stefania Ceruti and Walter Malorni and Flaminio Cattabeni and Abbracchio, {Maria P.}",
year = "2000",
month = "7",
day = "3",
doi = "10.1016/S0165-1838(00)00152-1",
language = "English",
volume = "81",
pages = "3--9",
journal = "Autonomic Neuroscience: Basic and Clinical",
issn = "1566-0702",
publisher = "Elsevier",
number = "1-3",

}

TY - JOUR

T1 - A novel gliotic P2 receptor mediating cyclooxygenase-2 induction in rat and human astrocytes

AU - Brambilla, Roberta

AU - Ceruti, Stefania

AU - Malorni, Walter

AU - Cattabeni, Flaminio

AU - Abbracchio, Maria P.

PY - 2000/7/3

Y1 - 2000/7/3

N2 - In astrocytic cultures maintained in vitro, a brief challenge with the ATP analog α,βmethyleneATP (α,βmeATP) results, 3 days later, in marked elongation of astrocytic processes, an event that resembles the astrocytic hypertrophy known to occur in vivo during reactive astrogliosis. α,βmeATP- induced effects were observed in primary astrocytes obtained from both rat striatum and cortex (a brain area highly involved in chronic neurodegenerative pathologies), as well as in human astrocytoma cells (ADF cells). Purine-induced gliosis could be reversed by the non-selective P2X/P2Y receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), but not by oxidized ATP (an antagonist of the P2X7 receptor), in line with previous studies of our laboratory suggesting the involvement of a P2Y receptor subtype. Induction of reactive gliosis was preceded by increased expression of cyclooxygenase-2 (COX-2), an enzyme whose excessive activation has been implicated in both acute and chronic neurodegenerative diseases. The selective COX-2 inhibitor NS-398 prevented both purine-induced astrogliosis and the associated COX-2 induction, suggesting that inhibition of the transcription of the COX-2 gene may also contribute to the anti-inflammatory properties of this agent. Significant blockade of both α,βmeATP-mediated reactive gliosis and COX-2 induction was also observed with PPADS. These data suggest that COX-2 mediates P2Y receptor-induced reactive astrogliosis, and that antagonists selective for this receptor subtype may represent a novel class of anti-inflammatory agents of potential interest in acute and chronic neurological disorders characterized by an inflammatory component and reactive gliosis. (C) 2000 Elsevier Science B.V.

AB - In astrocytic cultures maintained in vitro, a brief challenge with the ATP analog α,βmethyleneATP (α,βmeATP) results, 3 days later, in marked elongation of astrocytic processes, an event that resembles the astrocytic hypertrophy known to occur in vivo during reactive astrogliosis. α,βmeATP- induced effects were observed in primary astrocytes obtained from both rat striatum and cortex (a brain area highly involved in chronic neurodegenerative pathologies), as well as in human astrocytoma cells (ADF cells). Purine-induced gliosis could be reversed by the non-selective P2X/P2Y receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), but not by oxidized ATP (an antagonist of the P2X7 receptor), in line with previous studies of our laboratory suggesting the involvement of a P2Y receptor subtype. Induction of reactive gliosis was preceded by increased expression of cyclooxygenase-2 (COX-2), an enzyme whose excessive activation has been implicated in both acute and chronic neurodegenerative diseases. The selective COX-2 inhibitor NS-398 prevented both purine-induced astrogliosis and the associated COX-2 induction, suggesting that inhibition of the transcription of the COX-2 gene may also contribute to the anti-inflammatory properties of this agent. Significant blockade of both α,βmeATP-mediated reactive gliosis and COX-2 induction was also observed with PPADS. These data suggest that COX-2 mediates P2Y receptor-induced reactive astrogliosis, and that antagonists selective for this receptor subtype may represent a novel class of anti-inflammatory agents of potential interest in acute and chronic neurological disorders characterized by an inflammatory component and reactive gliosis. (C) 2000 Elsevier Science B.V.

KW - Cyclooxygenase-2

KW - Neurodegeneration

KW - P2 receptors

KW - Reactive astrogliosis

UR - http://www.scopus.com/inward/record.url?scp=0034601224&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034601224&partnerID=8YFLogxK

U2 - 10.1016/S0165-1838(00)00152-1

DO - 10.1016/S0165-1838(00)00152-1

M3 - Article

C2 - 10869693

AN - SCOPUS:0034601224

VL - 81

SP - 3

EP - 9

JO - Autonomic Neuroscience: Basic and Clinical

JF - Autonomic Neuroscience: Basic and Clinical

SN - 1566-0702

IS - 1-3

ER -