Modulation by calcium/calmodulin-dependent protein kinase II of functional response of delta opioid receptor in neuroblastoma x glioma hybrid (NG108-15) cells

G. H. Fan, Wenbo Zhang, C. P. Yao, G. Pei

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The potential modulation of opioid receptor signaling by calcium/calmodulin-dependent protein kinase II (CaMKII) has been investigated in NG108-15 cells. Both CaMKII specific inhibitors used, KN62 and KN93, time- and dose-dependently blocked inhibition of cAMP accumulation by [D-Pen2,D-Pen5]enkephalin (DPDPE), with an IC50 of about 1.2 μM and 0.8 μM, respectively. In the presence of 1 μM KN62 or KN93, the DPDPE dose-response curve shifted to the right (IC50 from 0.7 to 20 nM for KN62 and from 0.65 to 10 nM for KN93, respectively), and the maximal response was also significantly reduced. KN92, an inactive analogue of KN93, showed no significant impact, while ionomycin, an activator of CaMKII, greatly potentiated the opioid receptor response, suggesting that the effects of KN62, KN93 and ionomycin were likely mediated through CaMKII. In addition, KN62 did not affect ligand binding, receptor/Gi coupling, or basal and forskolin-stimulated adenylyl cyclase activity, suggesting its possible interference in the Gi/adenylyl cyclase interaction. Furthermore, a CaMKII inhibitor potently blocked the functional responses of other Gi-coupled receptors (m4 muscarinic and alpha2 adrenergic receptors) tested, but not that of Gs-coupled receptors (prostaglandin E1 and adenosine receptors). Our results clearly demonstrate that CaMKII modulates the signaling of opioid receptor and other Gi-coupled receptors.

Original languageEnglish (US)
Pages (from-to)1763-1769
Number of pages7
JournalNeuropharmacology
Volume36
Issue number11-12
DOIs
StatePublished - Nov 1997
Externally publishedYes

Fingerprint

Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases
delta Opioid Receptor
Neuroblastoma
Glioma
Opioid Receptors
D-Penicillamine (2,5)-Enkephalin
Ionomycin
Adenylyl Cyclases
Inhibitory Concentration 50
Muscarinic M4 Receptors
Prostaglandin Receptors
Purinergic P1 Receptors
Alprostadil
Colforsin
Protein Kinase Inhibitors
Adrenergic Receptors
Ligands

Keywords

  • Calcium/calmodulin-dependent protein kinase II
  • Delta opioid receptor
  • Ionomycin
  • KN62
  • KN92
  • KN93

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Modulation by calcium/calmodulin-dependent protein kinase II of functional response of delta opioid receptor in neuroblastoma x glioma hybrid (NG108-15) cells. / Fan, G. H.; Zhang, Wenbo; Yao, C. P.; Pei, G.

In: Neuropharmacology, Vol. 36, No. 11-12, 11.1997, p. 1763-1769.

Research output: Contribution to journalArticle

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abstract = "The potential modulation of opioid receptor signaling by calcium/calmodulin-dependent protein kinase II (CaMKII) has been investigated in NG108-15 cells. Both CaMKII specific inhibitors used, KN62 and KN93, time- and dose-dependently blocked inhibition of cAMP accumulation by [D-Pen2,D-Pen5]enkephalin (DPDPE), with an IC50 of about 1.2 μM and 0.8 μM, respectively. In the presence of 1 μM KN62 or KN93, the DPDPE dose-response curve shifted to the right (IC50 from 0.7 to 20 nM for KN62 and from 0.65 to 10 nM for KN93, respectively), and the maximal response was also significantly reduced. KN92, an inactive analogue of KN93, showed no significant impact, while ionomycin, an activator of CaMKII, greatly potentiated the opioid receptor response, suggesting that the effects of KN62, KN93 and ionomycin were likely mediated through CaMKII. In addition, KN62 did not affect ligand binding, receptor/Gi coupling, or basal and forskolin-stimulated adenylyl cyclase activity, suggesting its possible interference in the Gi/adenylyl cyclase interaction. Furthermore, a CaMKII inhibitor potently blocked the functional responses of other Gi-coupled receptors (m4 muscarinic and alpha2 adrenergic receptors) tested, but not that of Gs-coupled receptors (prostaglandin E1 and adenosine receptors). Our results clearly demonstrate that CaMKII modulates the signaling of opioid receptor and other Gi-coupled receptors.",
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