Attenuation of delta opioid receptor-mediated signaling by kainic acid in neural cells: involvement of protein kinase C and intracellular Ca2+

The potential modulation of opioid receptor signaling by kainic acid (KA) h as been investigated in neuroblastoma x glioma NG 108-15 hybrid cells and n euroblastoma SK-N-SH cells. Acute incubation of KA significantly attenuated delta opioid receptor (DOR) signaling induced by the DOR agonist [D-Pen(2) , D-Pen(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, su ggesting possible mediation through kainate/AMPA receptors. KA attenuation of DPDPE-stimulated G protein activation tvas reversed by inhibitors of pro tein kinase C or by removal of both extracellular Ca2+ and intracellular Ca 2+. In contrast, NMDA attenuation of DPDPE-stimulated G protein activation was independent of intracellular Ca2+, indicating that different mechanism( s) may underlie the modulation effect of KA and NMDA. This notion was furth er supported by the results that KA did not alter nociceptin/orphanin FQ-st imulated 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 evi dence that KA may be involved in the modulation of opioid receptor signal t ransduction. (C) 1999 Elsevier Science Ltd. All rights reserved.