Attenuation of delta opioid receptor-mediated signaling by kainic acid in neural cells: involvement of protein kinase C and intracellular Ca super(2+)

• Published in: Neuropharmacology 1999-07, Vol.38 (7), p.991-998
• Main Authors: Ben, L-H, Zhao, J, Xin, S-M, Luo, S-Q, Pei, G
• Format: Article
• Language: English
• Subjects: kainic acid
• ISSN: 0028-3908

The potential modulation of opioid receptor signaling by kainic acid (KA) has been investigated in neuroblastoma x glioma NG 108-15 hybrid cells and neuroblastoma SK-N-SH cells. Acute incubation of KA significantly attenuated delta opioid receptor (DOR) signaling induced by the DOR agonist [D-Pen super(2), D-Pen super(5)]-enkephalin (DPDPE), as measured by activation of G proteins and inhibition of cAMP accumulation. The attenuation by KA was time- and dose-dependent and could be blocked by antagonists of kainate/AMPA receptors, suggesting possible mediation through kainate/AMPA receptors. KA attenuation of DPDPE-stimulated G protein activation was reversed by inhibitors of protein kinase C or by removal of both extracellular Ca super(2+) and intracellular Ca super(2+). In contrast, NMDA attenuation of DPDPE-stimulated G protein activation was independent of intracellular Ca super(2+), indicating that different mechanism(s) may underlie the modulation effect of KA and NMDA. This notion was further supported by the results that KA did not alter nociceptin/orphanin FQ-stimulated G protein activation in NG 108-15 cells but NMDA did. In addition, pretreatment of NG 108-15 cells with antagonists of kainate/AMPA receptors blocked the acute desensitization of DOR signaling. These data provide evidence that KA may be involved in the modulation of opioid receptor signal transduction.