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Nucleotide‐mediated calcium signaling in rat cortical astrocytes: Role of P2X and P2Y receptors
Author(s) -
Fumagalli Marta,
Brambilla Roberta,
D'Ambrosi Nadia,
Volonté Cinzia,
Matteoli Michela,
Verderio Claudia,
Abbracchio Maria P.
Publication year - 2003
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.10248
Subject(s) - p2y receptor , ppads , p2 receptor , receptor , biology , suramin , agonist , astrocyte , purinergic receptor , microbiology and biotechnology , biochemistry , endocrinology , central nervous system
ATP is the dominant messenger for astrocyte‐to‐astrocyte calcium‐mediated communication. Definition of the exact ATP/P2 receptors in astrocytes and of their coupling to intracellular calcium ([Ca 2+ ] i ) has important implications for brain physiology and pathology. We show that, with the only exception of the P2X 6 receptor, primary rat cortical astrocytes express all cloned ligand‐gated P2X (i.e., P2X 1–5 and P2X 7 ) and G‐protein‐coupled P2Y receptors (i.e., P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 , and P2Y 12 ). These cells also express the P2Y‐like UDP‐glucose receptor, which has been recently recognized as the P2Y 14 receptor. Single‐cell image analysis showed that only some of these receptors are coupled to [Ca 2+ ] i . While ATP induced rapid and transient [Ca 2+ ] i increases (counteracted by the P2 antagonists suramin, pyridoxal‐phosphate‐6‐azophenyl‐2′‐4′‐disulfonic acid and oxidized ATP), the P2X 1 /P2X 3 agonist αβmeATP produced no changes. Conversely, the P2X 7 agonist BzATP markedly increased [Ca 2+ ] i ; the presence and function of the P2X 7 receptor was also confirmed by the formation of the P2X 7 pore. ADP and 2meSADP also produced [Ca 2+ ] i increases antagonized by the P2Y 1 antagonist MRS2179. Some cells also responded to UTP but not to UDP. Significant responses to sugar‐nucleotides were also detected, which represents the first functional response reported for the putative P2Y 14 receptor in a native system. Based on agonist preference of known P2 receptors, we conclude that, in rat astrocytes, ATP‐induced calcium rises are at least mediated by P2X 7 and P2Y 1 receptors; additional receptors (i.e., P2X 2 , P2X 4 , P2X 5 , P2Y 2 , P2Y 4 , and P2Y 14 ) may also contribute. © 2003 Wiley‐Liss, Inc.