P2Y(1) purinoceptor-mediated Ca(2+) signaling and Ca(2+) wave propagation in dorsal spinal cord astrocytes.
ATP is known to act as an extracellular messenger mediating the propagation of Ca(2+) waves in astrocyte networks. ATP mediates Ca(2+) waves by activating P2Y purinoceptors, which mobilize intracellular Ca(2+) in astrocytes. A number of P2Y purinoceptor subtypes have been discovered, but it is not known which P2Y subtypes participate in transmitting astrocyte Ca(2+) waves. Here, we show that ATP analogs that are selective agonists for the P2Y(1) subtype of purinoceptor caused release of intracellular Ca(2+) in astrocytes from the dorsal spinal cord. The Ca(2+) responses were blocked by adenosine-3'-phospho-5'-phosphosulfate, an antagonist known to selectively inhibit P2Y(1) but not other P2Y purinoceptor subtypes. Also, we show that P2Y(1) mRNA is expressed in dorsal spinal cord astrocytes. Furthermore, expression of P2Y(1) in an astrocytoma cell line lacking endogenous purinoceptors was sufficient to permit propagation of intercellular Ca(2+) waves. Finally, Ca(2+) wave propagation in dorsal spinal cord astrocytes was suppressed by pharmacologically blocking P2Y(1) purinoceptors. Together, these results indicate that dorsal spinal astrocytes express functional P2Y(1) purinoceptors, which participate in the transmission of Ca(2+) waves. Ca(2+) waves in astrocytes have been implicated as a major signaling pathway coordinating glial and neuronal activity; therefore, P2Y(1) purinoceptors may represent an important link in cell-cell signaling in the CNS.
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S R
SR
Programme in Brain and Behaviour, Hospital For Sick Children, University of Toronto, Toronto, Ontario M5G 1X8, Canada.
Gallagher
C J
CJ
Salter
M W
MW
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005260:Female; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D058472:Receptors, Purinergic P2Y1; D013873:Thionucleotides / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology
D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D013873:Thionucleotides; C002480:methylthio-ADP; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D002118:Calcium; D014544:Uridine Triphosphate; C008501:2-methylthio-ATP