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• W1918384039 endingPage "5828" @default.
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• W1918384039 abstract "One of the major responses upon orexin receptor activation is Ca(2+) influx, and this influx seems to amplify the other responses mediated by orexin receptors. However, the reduction in Ca(2+) , often used to assess the importance of Ca(2+) influx, might affect other properties, like ligand-receptor interactions, as suggested for some GPCR systems. Hence, we investigated the role of the ligand-receptor interaction and Ca(2+) signal cascades in the apparent Ca(2+) requirement of orexin-A signalling.Receptor binding was assessed in CHO cells expressing human OX1 receptors with [(125) I]-orexin-A by conventional ligand binding as well as scintillation proximity assays. PLC activity was determined by chromatography.Both orexin receptor binding and PLC activation were strongly dependent on the extracellular Ca(2+) concentration. The relationship between Ca(2+) concentration and receptor binding was the same as that for PLC activation. However, when Ca(2+) entry was reduced by depolarizing the cells or by inhibiting the receptor-operated Ca(2+) channels, orexin-A-stimulated PLC activity was much more strongly inhibited than orexin-A binding.Ca(2+) plays a dual role in orexin signalling by being a prerequisite for both ligand-receptor interaction and amplifying orexin signals via Ca(2+) influx. Some previous results obtained utilizing Ca(2+) chelators have to be re-evaluated based on the results of the current study. From a drug discovery perspective, further experiments need to identify the target for Ca(2+) in orexin-A-OX1 receptor interaction and its mechanism of action." @default.
• W1918384039 created "2016-06-24" @default.
• W1918384039 creator A5050598846 @default.
• W1918384039 creator A5080765918 @default.
• W1918384039 creator A5085009570 @default.
• W1918384039 date "2014-11-05" @default.
• W1918384039 modified "2023-10-16" @default.
• W1918384039 title "Calcium affects <scp>OX</scp>₁ orexin (hypocretin) receptor responses by modifying both orexin binding and the signal transduction machinery" @default.
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• W1918384039 doi "https://doi.org/10.1111/bph.12883" @default.
• W1918384039 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4290719" @default.
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• W1918384039 hasPublicationYear "2014" @default.
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