Cyclic AMP regulates the calcium transients released form IP3-sensitive stores by activation of rat κ-opioid receptors expressed in CHO cells

M. Ikeda, C. S. Nelson, H. Shinagawa, T. Shinoe, T. Sugiyama, C. N. Allen, D. K. Grandy, T. Yoshioka

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

We analyzed intracellular Ca2+ and cAMP levels in Chinese hamster ovary cells expressing a cloned rat kappa opioid receptor (CHO-κ cells). Although expression of kappa (κ)-opioid receptors was confirmed with a fluorescent dynorphin analog in almost all CHO-κ cells, the κ-specific agonists, U50488H or U69593, induced a Ca2+ transient only in 35% of the cells. The Ca2+ response occurred in all-or-none fashion and the half-maximal dosage of U50488H (812.1 nM) was higher than that (3.2 nM) to inhibit forskolin-stimulated cAMP. The κ-receptors coupled to Gi/o proteins since pertussis toxin significantly reduced the U50488H actions on intracellular Ca2+ and cAMP. The Ca2+ transient originates from IP3-sensitive internal stores since the Ca2+ response was blocked by a PLC inhibitor (U73122) or by thapsigargin depletion of internal stores while removal of extracellular Ca2+ had no effect. Interestingly, application of dibutyryl cAMP (+56.2%) or 8-bromo-cAMP (+ 174.7%) significantly increased the occurrence of U50488H-induced Ca2+ mobilization while protein kinase A (PKA) inhibitors, Rp-cAMP (-32.3%) or myr-Ψ PKA (-73.9%) significantly reduced the response. Therefore, it was concluded that cAMP and PKA activity can regulate the Ca2+ mobilization. These results suggest that the κ receptor-linked cAMP cascade regulates the occurrence of κ-opioid-mediated Ca2+ mobilization.

Original languageEnglish (US)
Pages (from-to)39-48
Number of pages10
JournalCell Calcium
Volume29
Issue number1
DOIs
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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