D-erythro-Sphingosine (synthetic)

Sphingosine inhibition and promotion of histamine release from isolated rat mast cells.[Pubmed:1707581]

Agents Actions. 1990 Nov;31(3-4):171-67.

Sphingosine inhibited the histamine release induced by antigen, compound 48/80 with and without calcium, and the combination of TPA and the ionophore A23187. The inhibition occurred in the concentration range 1-3 microM, where no sign of cytotoxicity was noted. Preincubation for 5-10 min was needed for inhibition, and the effect persisted after washing of the cells. No inhibition was found with optimal concentrations of the ionophore or with TPA present during the preincubation. Sphingosine in combination with suboptimal concentrations of the ionophore could induce a considerable histamine release. This response was dependent on energy and was potently inhibited by the flavonoid phloretin. After preincubation with TPA, sphingosine exerted a pronounced potentiation of the response to very low concentrations of the ionophore. The findings regarding inhibitory effects of sphingosine do not seem to be compatible with a selective action on protein kinase C. The ability to synergize with the ionophore and to potentiate the effect of preincubation with TPA resembles previous findings with palmitoylcarnitine and suggests that sphingosine can stimulate mast cells by activation of protein kinase C.

Structural requirements for long-chain (sphingoid) base inhibition of protein kinase C in vitro and for the cellular effects of these compounds.[Pubmed:2742830]

Biochemistry. 1989 Apr 18;28(8):3138-45.

Sphingosine, sphinganine, and other long-chain (sphingoid) bases inhibit protein kinase C in vitro and block cellular responses to agonists that are thought to act via this enzyme. To gain further insight into the mechanism of this inhibition, a series of long-chain analogues differing in alkyl chain length (11-20 carbon atoms), stereochemistry, and headgroup were examined for (a) inhibition of protein kinase C activity in vitro, (b) the neutrophil respiratory burst in response to phorbol myristate acetate (PMA), (c) the PMA-induced differentiation of HL-60 cells, and (d) the growth of Chinese hamster ovary cells. In every instance, the effects were maximal with the 18-carbon homologues, which are the same length as the predominant naturally occurring long-chain base (sphingosine). The lower potency of the shorter chain homologues was partially due to decreased uptake by cells. Small differences were obtained with the four stereoisomers of sphingosine (i.e., D and L forms of erythro- and threo-sphingosine), with N-methyl derivatives of the different sphingosine homologues, and with simpler alkylamines (e.g., stearylamine). The potency of the different headgroup analogues may be affected by the degree of protonation at the assay pH. The pKa of sphingosine was measured to be 6.7; the pKa varied among the analogues. These findings establish that the major structural features required for inhibition of protein kinase C and cellular processes dependent on this enzyme are the presence of a free amino group and an aliphatic side chain and that other groups have more subtle effects.(ABSTRACT TRUNCATED AT 250 WORDS)

D-erythro-Sphingosine (Erythrosphingosine) is a very potent activator of p32-kinase with an EC50 of 8 μM, and inhibits protein kinase C (PKC). D-erythro-Sphingosine (Erythrosphingosine) is also a PP2A activator.

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