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) 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-Pen2, D-Pen5]-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 Ca2+ and intracellular Ca2+. 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 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.
Ben
L H
LH
Shanghai Institute of Cell Biology and Shanghai Research Center of Life Sciences, Chinese Academy of Sciences, Peoples Republic of China.
Zhao
J
J
Xin
S M
SM
Luo
S Q
SQ
Pei
G
G
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D000094942:Nociceptin Receptor
D004745:Enkephalins; D018690:Excitatory Amino Acid Agonists; D018091:Receptors, AMPA; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D020881:Enkephalin, D-Penicillamine (2,5)-; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D007608:Kainic Acid; D002118:Calcium; D000094942:Nociceptin Receptor; C000722287:Oprl1 protein, mouse