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Intracellular Ca(2+) signals provide astrocytes with a specific form of excitability that enables them to regulate synaptic transmission. In this study, we demonstrate that NAADP-AM, a membrane-permeant analogue of the new second messenger nicotinic acid-adenine dinucleotide phosphate (NAADP), mobilizes Ca(2+) in astrocytes and that the response is blocked by Ned-19, an antagonist of NAADP signalling. We also show that NAADP receptors are expressed in lysosome-related acidic vesicles. Pharmacological disruption of either NAADP or lysosomal signalling reduced Ca(2+) responses induced by ATP and endothelin-1, but not by bradykinin. Furthermore, ATP increased endogenous NAADP levels. Overall, our data provide evidence for NAADP being an intracellular messenger for agonist-mediated calcium signalling in astrocytes.

Original publication

DOI

10.1016/j.febslet.2011.05.062

Type

Journal article

Journal

FEBS Lett

Publication Date

21/07/2011

Volume

585

Pages

2300 - 2306

Keywords

Adenosine Triphosphate, Animals, Astrocytes, Bradykinin, Calcium, Calcium Signaling, Cells, Cultured, Chelating Agents, Egtazic Acid, Endothelin-1, NADP, Rats, Rats, Sprague-Dawley