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CCK-8 enhances acid-sensing ion channel currents in rat primary sensory neurons. | LitMetric

CCK-8 enhances acid-sensing ion channel currents in rat primary sensory neurons.

Neuropharmacology

School of Pharmacy, School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, 88 Xianning Road, Xianning 437100, Hubei, PR China; Department of Physiology, Hubei College of Chinese Medicine, 87 Xueyuan Road, Jingzhou 434020, Hubei, PR China. Electronic address:

Published: December 2023

AI Article Synopsis

  • Cholecystokinin (CCK) is a peptide involved in pain modulation, and this study explores its relationship with acid-sensitive ion channels (ASICs) in pain processes.
  • The researchers found that CCK-8 increases acid-evoked ASIC currents in rat dorsal root ganglion (DRG) neurons through the activation of the CCK2 receptor (CCK2R), relying on G-proteins and protein kinase C (PKC) signaling.
  • Moreover, CCK-8 exacerbates pain behavior in rats during acid exposure, highlighting CCK-8/CCK2R as a potential target for pain therapy relating to ASIC activation.

Article Abstract

Cholecystokinin (CCK) is a peptide that has been implicated in pain modulation. Acid sensitive ion channels (ASICs) also play an important role in pain associated with tissue acidification. However, it is still unclear whether there is an interaction between CCK signaling and ASICs during pain process. Herein, we report that a functional link between them in rat dorsal root ganglion (DRG) neurons. Pretreatment with CCK-8 concentration-dependently increased acid-evoked ASIC currents. CCK-8 increased the maximum response of ASICs to acid, but did not changed their acid sensitivity. Enhancement of ASIC currents by CCK-8 was mediated by the stimulation of CCK2 receptor (CCK2R), rather than CCK1R. The enhancement of ASIC currents by CCK-8 was prevented by application of either G-protein inhibitor GDP-β-S or protein kinase C (PKC) inhibitor GF109203×, but not by protein kinase A (PKA) inhibitor H-89 or JNK inhibitor SP600125. Moreover, CCK-8 increased the number of action potentials triggered by acid stimuli by activating CCK2R. Finally, CCK-8 dose-dependently exacerbated acid-induced nociceptive behavior in rats through local CCK2R. Together, these results indicated that CCK-8/CCK2R activation enhanced ASIC-mediated electrophysiological activity in DRG neurons and nociception in rats. The enhancement effect depended on G-proteins and intracellular PKC signaling rather than PKA and JNK signaling pathway. These findings provided that CCK-8/CCK2R is an important therapeutic target for ASIC-mediated pain.

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Source
http://dx.doi.org/10.1016/j.neuropharm.2023.109739DOI Listing

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