Desensitization of δ-opioid-induced mobilization of Ca2+ stores in NG108-15 cells

Shin Hee Yoon, Wenzhen Jin, Robert J. Spencer, Horace H Loh, Stanley A Thayer

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14 Scopus citations

Abstract

Activation of δ-opioid receptors in NG108-15 cells induces the release of calcium from an inositol 1,4,5-trisphosphate-sensitive intracellular store. We used fura-2-based digital imaging to study the effects of prolonged exposure to agonist on opioid-induced increases in [Ca2+](i). Exposure to D-Ala2-D-Leu5 enkephalin (DADLE) (1 μM) for 30 min completely desensitized NG108-15 cells to a second DADLE-induced response. The cells recovered gradually over 25 min following washout of DADLE. The desensitization was not due to depletion of intracellular calcium stores and bradykinin failed to cross-desensitize the DADLE-evoked response, although both agonists mobilized the same Ca2+ store. Desensitization induced by 100 nM DADLE was overcome by a higher concentration of DADLE (100 μM). Treatment with 8-cpt-cAMP (0.1 mM) for 30 min did not influence the DADLE-induced increases in [Ca2+ ](i). Phorbol dibutyrate (PdBu) (1 μM) blocked the response completely. Treatment with the inhibitor of cyclic nucleotide-dependent kinases H8 (1 μM) for 45 min did not prevent DADLE-induced desensitization. Treatment with the protein kinase C (PKC) inhibitors staurosporin (10 nM) and GF-109203X (200 nM) for 45 min reduced desensitization. However, down-regulation of PKC by 24 h exposure to PdBu (1 μM) failed to prevent the DADLE-induced desensitization in NG108- 15 cells. Thus, we conclude that multiple pathways participated in desensitization of δ-receptor-mediated Ca2+ mobilization, one of which includes PKC.

Original languageEnglish (US)
Pages (from-to)9-18
Number of pages10
JournalBrain Research
Volume802
Issue number1-2
DOIs
StatePublished - Sep 17 1998

Bibliographical note

Funding Information:
This work was supported by grants from the National Institute on Drug Abuse (DA09293, DA07304, DA01583, DA05695, DA07339) and the National Science Foundation (IBN9723796). SHY was supported by a fellowship from the Korea Science and Engineering Foundation and leave from Catholic University Medical College, Seoul, Korea.

Keywords

  • Ca store
  • DADLE
  • IP
  • Intracellular Ca
  • Kinase
  • Opioid
  • δ receptor

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