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Immunoreactivity for glial fibrillary acidic protein and P2 receptor expression on astrocytes in vivo
Author(s) -
Franke Heike,
Krügel Ute,
Grosche Jens,
Illes Peter
Publication year - 2003
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10216
Subject(s) - ppads , glial fibrillary acidic protein , p2 receptor , receptor , p2y receptor , agonist , astrocyte , endocrinology , medicine , biology , chemistry , receptor antagonist , antagonist , biochemistry , central nervous system , immunohistochemistry
Changes in glial fibrillary acidic protein (GFAP) are believed to be a sensitive and specific marker for astroglial responses to various kinds of injury. Neurotrophic factors and their receptors involved in the physiological and pathological responses of astrocytes are of special interest. For example, ATP, released from damaged or dying cells, may represent one of the endogenous factors mediating the activation of astrocytes. In the present study, the influence of different ATP analogs on the GFAP‐immunoreactivity (IR) and on the expression of P2 receptors on GFAP‐labeled cells were studied. Microinjection of the selective P2 receptor agonists α,β‐methylene ATP (α,β‐meATP; P2X 1,3 ), adenosine 5′‐O‐(2‐thiodiphosphate) (ADP‐β‐S; P2Y 1,12 ), and uridine 5′‐O‐(3‐thiotriphosphate) (UTP‐γ‐S; P2Y 2,4,6 ) in the nucleus accumbens (NAc) of rats resulted in an increase of GFAP‐IR in comparison to the treatment with artificial cerebrospinal fluid. The agonist‐induced morphogenic changes documented a strong potency of α,β‐meATP and ADP‐β‐S. The effect of UTP‐γ‐S was small. Blockade of P2 receptors with the nonselective antagonist pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS) decreased the injury‐induced elevation of GFAP‐IR when given alone and in addition inhibited the agonist effects. Double immunofluorescence measurements confined the localization of P2X 2–4 and P2Y 1 receptor subtypes to GFAP‐labeled astrocytes of untreated rats. The receptor subtypes P2X 1,5,7 were not present in the NAc of native rats, but became expressed after mechanical damage. P2X 6 receptor‐labeling was absent both with and without mechanical damage. After microinjection of α,β‐meATP and ADP‐β‐S into the NAc, the P2X 1,3 ‐ and P2Y 1 ‐IR, respectively, appeared to increase. These results show that the stimulation of P2 receptors influences the expression of GFAP‐IR in vivo. GFAP‐positive astrocytes possess P2X as well as P2Y receptor subtypes and change the expression of these receptors after injury and subsequent long‐term activation by ATP. Drug Dev. Res. 59:175–189, 2003. © 2003 Wiley‐Liss, Inc.