Nucleotide-mediated calcium signaling in rat cortical astrocytes: Role of P2X and P2Y receptors

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 ([Ca2+]i) has important implications for brain physiology and pathology. We show that, with the only exceptio...

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Published in:Glia 2003-09, Vol.43 (3), p.218-230
Main Authors: Fumagalli, Marta, Brambilla, Roberta, D'Ambrosi, Nadia, Volonté, Cinzia, Matteoli, Michela, Verderio, Claudia, Abbracchio, Maria P.
Format: Article
Language:English
Subjects:
adenine and uridine nucleotides
Adenosine Diphosphate - analogs & derivatives
Adenosine Diphosphate - pharmacology
Adenosine Triphosphate - agonists
Adenosine Triphosphate - analogs & derivatives
Adenosine Triphosphate - metabolism
Adenosine Triphosphate - pharmacology
Animals
Animals, Newborn
astrocytes
Astrocytes - cytology
Astrocytes - drug effects
Astrocytes - metabolism
Biological and medical sciences
calcium signaling
Calcium Signaling - drug effects
Calcium Signaling - genetics
Cells, Cultured
Cerebral Cortex - cytology
Cerebral Cortex - metabolism
Fundamental and applied biological sciences. Psychology
Homeostasis - drug effects
Homeostasis - genetics
Isolated neuron and nerve. Neuroglia
Nucleotides - metabolism
P2X receptors
P2Y receptors
Rats
Receptors, G-Protein-Coupled - genetics
Receptors, G-Protein-Coupled - metabolism
Receptors, Purinergic P2 - drug effects
Receptors, Purinergic P2 - genetics
Receptors, Purinergic P2 - metabolism
Receptors, Purinergic P2X
Receptors, Purinergic P2Y1
UDP-glucose
Vertebrates: nervous system and sense organs
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Summary: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 ([Ca2+]i) has important implications for brain physiology and pathology. We show that, with the only exception of the P2X6 receptor, primary rat cortical astrocytes express all cloned ligand‐gated P2X (i.e., P2X1–5 and P2X7) and G‐protein‐coupled P2Y receptors (i.e., P2Y1, P2Y2, P2Y4, P2Y6, and P2Y12). These cells also express the P2Y‐like UDP‐glucose receptor, which has been recently recognized as the P2Y14 receptor. Single‐cell image analysis showed that only some of these receptors are coupled to [Ca2+]i. While ATP induced rapid and transient [Ca2+]i increases (counteracted by the P2 antagonists suramin, pyridoxal‐phosphate‐6‐azophenyl‐2′‐4′‐disulfonic acid and oxidized ATP), the P2X1/P2X3 agonist αβmeATP produced no changes. Conversely, the P2X7 agonist BzATP markedly increased [Ca2+]i; the presence and function of the P2X7 receptor was also confirmed by the formation of the P2X7 pore. ADP and 2meSADP also produced [Ca2+]i increases antagonized by the P2Y1 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 P2Y14 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 P2X7 and P2Y1 receptors; additional receptors (i.e., P2X2, P2X4, P2X5, P2Y2, P2Y4, and P2Y14) may also contribute. © 2003 Wiley‐Liss, Inc.
ISSN:0894-1491
1098-1136
DOI:10.1002/glia.10248