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Ceramide selectively inhibits calcium-mediated potentiation of beta-adrenergic-stimulated cyclic nucleotide accumulation in rat pinealocytes



Ceramide selectively inhibits calcium-mediated potentiation of beta-adrenergic-stimulated cyclic nucleotide accumulation in rat pinealocytes



Biochemical and Biophysical Research Communications 244(1): 57-61



Interaction between sphingomyelin metabolism and cyclic nucleotide synthesis in rat pinealocytes was investigated by determining the effect of ceramide on adrenergic-stimulated cAMP and cGMP accumulation. Although C2-, C6-, and C8-ceramide had no effect on basal, isoproterenol-, or norepinephrine-stimulated cAMP and cGMP accumulation, they inhibited the potentiation caused by depolarising concentrations of K+ or BayK 8644. Similar inhibition was observed when ceramide metabolism was inhibited by a glucosylceramide synthase inhibitor. In contrast, the potentiation of cAMP and cGMP accumulation caused by other intracellular Ca(2+)-elevating agents such as ionomycin or thapsigargin or by an activator of protein kinase C was not affected by ceramide. Taken together, our results suggest that ceramide selectively inhibits cyclic nucleotide synthesis when the nucleotide synthesis is potentiated by an increase in intracellular Ca2+ through L-type Ca2+ channels and that the sphingomyelin cycle probably plays an important role in the regulation of these channels.

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Accession: 008278072

Download citation: RISBibTeXText

PMID: 9514888

DOI: 10.1006/bbrc.1998.8221


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