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Ceramide modulates nicotinic receptor‐dependent Ca 2+ signaling in rat chromaffin cells
Author(s) -
Liu Jihong,
Jorgensen Mark S.,
Adams Julye M.,
Titlow William B.,
NikolovaKarakashian Mariana,
Jackson Brian A.
Publication year - 2001
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.1246
Subject(s) - ceramide , chromaffin cell , staurosporine , endocrinology , medicine , catecholamine , sphingomyelin , nicotinic agonist , chemistry , signal transduction , thapsigargin , lipid signaling , biology , protein kinase c , microbiology and biotechnology , intracellular , receptor , adrenal medulla , biochemistry , apoptosis , cholesterol
Ceramide, which is an integral component of the sphingomyelin signaling pathway, can attenuate voltage‐gated Ca 2+ 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 Ca 2+ signaling and catecholamine secretion, in rat adrenal chromaffin cells. Short‐term C 6 ‐ceramide (CER) treatment dose‐dependently inhibited nicotine (NIC)‐induced peak intracellular Ca 2+ transients. Sphingomyelinase elicited similar responses, whereas the inactive ceramide analog C 2 ‐dihydroceramide had no effect on NIC‐induced Ca 2+ transients. CER suppressed KCl‐ and NIC‐induced Ca 2+ transients to a similar extent, suggesting that the voltage‐gated Ca 2+ 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 Ca 2+ currents. Pretreatment with staurosporine significantly attenuated CER‐dependent inhibition of both NIC‐induced Ca 2+ transients and peak Ca 2+ current, suggesting that the effects of CER are mediated at least in part by protein kinase C. Consistent with suppressed Ca 2+ 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 Ca 2+ signaling and catecholamine secretion in rat chromaffin cells. J. Neurosci. Res. 66:559–564, 2001. © 2001 Wiley‐Liss, Inc.