CERAMIDE SELECTIVELY INHIBITS CALCIUM-MEDIATED POTENTIATION OF BETA-ADRENERGIC-STIMULATED CYCLIC-NUCLEOTIDE ACCUMULATION IN RAT PINEALOCYTES

Interaction between sphingomyelin metabolism and cyclic nucleotide syn thesis in rat pinealocytes was investigated by determining the effect of ceramide on adrenergic-stimulated cAMP and cGMP accumulation. Altho ugh C2-, C6-, and C8-ceramide had no effect on basal, isoproterenol-, or norepinephrine-stimulated cAMP and cGMP accumulation, they inhibite d the potentiation caused by depolarising concentrations of K+ or BayK 8644. Similar inhibition was observed when ceramide metabolism was in hibited by a glucosylceramide synthase inhibitor, In contrast, the pot entiation of cAMP and cGMP accumulation caused by other intracellular Ca2+-elevating agents such as ionomycin or thapsigargin or by an activ ator of protein kinase C was not affected by ceramide, Taken together, our results suggest that ceramide selectively inhibits cyclic nucleot ide synthesis when the nucleotide synthesis is potentiated by an incre ase in intracellular Ca2+ through L-type Ca2+ channels and that the sp hingomyelin cycle probably plays an important role in the regulation o f these channels. (C) 1998 Academic Press.