TAILIEUCHUNG - Báo cáo khoa học: Factors affecting habituation of PC12 cells to ATP

Extracellular ATP triggers catecholamine secretion from PC12 cells by activating ionotropic purine receptors. Repeated stimulation by ATP leads to habituation of the secretory response. In this paper, we use amperometric detection to monitor the habituation of PC12 cells to mul-tiple stimulations of ATP or its agonist. Cells habituate to 30lMATP slower than they do to 300 or 600lMATP. Modifying external Mg2+ affects the response of cells to 30lMATP, but does not affect habituation, suggesting that habituation does not necessarily correspond to either sti-mulus intensity or cellular response. . | Eur. J. Biochem. 271 4034-4041 2004 FEBS 2004 doi Factors affecting habituation of PC12 cells to ATP J. Russel Keath1 and Edward W. Westhead2 1 Department Neurobiology and Physiology Northwestern University Evanston IL USA department of Biochemistry and Molecular Biology University of Massachusetts Amherst MA USA Extracellular ATP triggers catecholamine secretion from PC12 cells by activating ionotropic purine receptors. Repeated stimulation by ATP leads to habituation of the secretory response. In this paper we use amperometric detection to monitor the habituation of PC12 cells to multiple stimulations of ATP or its agonist. Cells habituate to 30 M ATP slower than they do to 300 or 600 M ATP. Modifying external Mg2 affects the response of cells to 30 M ATP but does not affect habituation suggesting that habituation does not necessarily correspond to either stimulus intensity or cellular response. Mg2 affects the initial response of PC12 cells to 2MeSATP in a manner similar to ATP. Increasing external Mg2 to mM however eliminates habituation to 2MeSATP. This habituation can be partially restored by costimulation with 100 M UTP. Background application of UTP increases habituation to both ATP and 2MeSATP. This suggests that ATP-sensitive metabotropic P2Y receptors play a role in the habituation process. Finally although Ca2 influx through voltage-operated calcium channels does not appear to contribute to secretion during ATP stimulation blocking these channels with nicardipine increases habituation. This suggests a role for voltage-operated calcium channels in the habituation process. Keywords voltage-operated calcium channels PC12 cells habituation inactivation P2X receptors. While ATP is commonly known as an energy storage molecule it also serves as a neurotransmitter. ATP activates both ionotropic P2X receptors triggering neurosecretion and metabotropic P2Y receptors which induce the production of inositol phosphates .

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