Ceramide modulates nicotinic receptor-dependent Ca2+ signaling in rat chromaffin cells

Jihong Liu, Mark S. Jorgensen, Julye M. Adams, William B. Titlow, Mariana Nikolova-Karakashian, Brian A. Jackson

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Ceramide, which is an integral component of the sphingomyelin signaling pathway, can attenuate voltagegated Ca2+ channel (VGCC) activity in a number of cell types. The aim of the present study was to determine whether ceramide can also modulate VGCC activity, and as a consequence nicotinic receptor-dependent Ca2+ signaling and catecholamine secretion, in rat adrenal chromaffin cells. Short-term C6-ceramide (CER) treatment dose-dependently inhibited nicotine (NIC)-induced peak intracellular Ca2+ transients. Sphingomyelinase elicited similar responses, whereas the inactive ceramide analog C2-dihydroceramide had no effect on NICinduced Ca2+ transients. CER suppressed KCl- and NICinduced Ca2+ transients to a similar extent, suggesting that the voltage-gated Ca2+ channel was a primary site of inhibition. In direct support of this concept, whole-cell patch-clamp analysis demonstrated that CER and sphingomyelinase significantly reduced peak Ca2+ currents. Pretreatment with staurosporine significantly attenuated CER-dependent inhibition of both NIC-induced Ca2+ transients and peak Ca2+ current, suggesting that the effects of CER are mediated at least in part by protein kinase C. Consistent with suppressed Ca2+ signaling, CER also significantly inhibited NIC-induced catecholamine secretion measured at the single-cell level by carbon fiber amperometry. This effect of CER was also significantly attenuated by pretreatment with staurosporine These data demonstrate that the sphingomyelin signaling pathway can modulate nicotinic receptor-dependent Ca2+ signaling and catecholamine secretion in rat chromaffin cells.

Original languageEnglish
Pages (from-to)559-564
Number of pages6
JournalJournal of Neuroscience Research
Issue number4
StatePublished - Nov 15 2001


  • Adrenal medulla
  • Ca channels
  • Catecholamines
  • Ceramide
  • Chromaffin cell
  • Intracellular Ca
  • Sphingomyelin

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience


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