Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 218, Issue 1-2, Pages 175-183Publisher
ELSEVIER SCI IRELAND LTD
DOI: 10.1016/j.mce.2003.10.048
Keywords
ceramide; Ca2+ channels; PKC; tyrosine kinase; GH(3) cells
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In this study, we investigated the effect of ceramide on the L-type Ca2+ channel (L-channel) in GH(3) cells. We found that C6-ceramide, but not C6-dihydroceramide, the inactive analogue, had an inhibitory effect on BayK 8644-stimulated GH release. Using patch clamp analysis, C6- and C2-ceramide, but not C6-dihydroceramide, were found to inhibit the L-channel current. Increasing intracellular ceramide level with sphingomyelinase also inhibited the L-channel current. The inhibitory effect of ceramide on the L-channel current was attenuated by calphostin C, a myristolated pseudosubstrate protein kinase C (PKC) inhibitor, and lavendustin A, a tyrosine kinase inhibitor. Combined treatment with lavendustin A and the myristolated PKC inhibitor blocked the effect of ceramide on the L-channel current. These results indicate that ceramide, a lipid messenger of the sphingomyelin pathway, is an important regulator of the L-channel in GH3 cells and both tyrosine kinase and PKC are involved in this effect of ceramide. (C) 2003 Elsevier Ireland Ltd. All rights reserved.
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