NAADP mediates ATP-induced Ca2+ signals in astrocytes

作者：Barcelo Torns Miquel; Lewis Alexander M; Gubern Albert; Barneda David; Bloor Young Duncan; Picatoste Fernado; Churchill Grant C; Claro Enrique; Masgrau Roser^*

来源：FEBS Letters, 2011, 585(14): 2300-2306.

DOI：10.1016/j.febslet.2011.05.062

• Lysosome
• Ca2+ mobilization
• Glia
• Endotehlin-1
• Bradykinin
• Ned-19

Intracellular Ca2+ 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 Ca2+ 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 Ca2+ 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.

• 出版日期2011-7-21