Caffeine does not inhibit substance P-evoked intracellular Ca2+ mobilization in rat salivary acinar cells

J. T. Seo, H. Sugiya, S. I. Lee, M. C. Steward, A. C. Elliott

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

We used the Ca2+-sensitive fluorescent dye fura 2, together with measurements of intracellular D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], to assess the inhibitory effects of caffeine on signal transduction via G protein-coupled receptor pathways in isolated rat mandibular salivary acinar cells. ACh, norepinephrine (NE), and substance P (SP) all evoked substantial increases in the intracellular free Ca2+ concentration ([Ca2+](i)). Responses to ACh and NE were markedly inhibited by prior application of 20 mM caffeine. The inhibitory effect of caffeine was not reproduced by phosphodiesterase inhibition with IBMX or addition of cell- permeant dibutyryl cAMP. In contrast to the ACh and NE responses, the [Ca2+](i) response to SP was unaffected by caffeine. Despite this, SP and ACh appeared to mobilize Ca2+ from a common intracellular pool. Measurements of agonist-induced changes in Ins(1,4,5)P3 levels confirmed that caffeine inhibited the stimulus-response coupling pathway at a point before Ins(1,4,5)P3 generation. Caffeine did not, however, inhibit [Ca2+](i) responses evoked by direct activation of G proteins with 40 mM F- . These data show that caffeine inhibits G protein-coupled signal transduction in these cells at some element that is common to the muscarinic and α-adrenergic signaling pathways but is not shared by the SP signaling pathway. We suggest that this element might be a specific structural motif on the G protein-coupled muscarinic and α-adrenergic receptors.

Original languageEnglish
Pages (from-to)C915-C922
JournalAmerican Journal of Physiology - Cell Physiology
Volume276
Issue number4 45-4
DOIs
Publication statusPublished - 1999

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

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