Sphingosine 1-phosphate enhances spontaneous transmitter release at the frog neuromuscular junction

Eugen Brailoiu, Robin L. Cooper, Nae J. Dun

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Intracellular recordings were made from isolated frog sciatic-sartorius nerve-muscle preparations, and the effects of sphingosine 1-phosphate (S1-P) on miniature endplate potentials (MEPPs) were studied. Extracellular application of S1-P (1 and 30 μM) had no significant effects on the frequency and amplitude of MEPPs. Delivery into nerve terminals by liposomes containing 10-5, 10-4 or 10-3 M S1-P was associated with a concentration-dependent increase in MEPP frequency of 37, 63 and 86%. The per cent of median MEPP amplitude was not significantly changed, but there was an increase in the number of 'giant' MEPPs. Pre-exposure of the preparations to S1-P 10-5 but not 10-8 M entrapped in liposomes for 15 min blocked the effects of subsequent superfusion of S1-P (10-4 M)-filled liposomes on MEPP frequency. Thus, intracellular S1-P receptors seem to undergo 'desensitization' to higher concentrations of S1-P. The result provides the first evidence that S1-P acting intracellularly but not extracellularly enhances spontaneous transmitter release at the frog neuromuscular junction.

Original languageEnglish
Pages (from-to)1093-1097
Number of pages5
JournalBritish Journal of Pharmacology
Volume136
Issue number8
DOIs
StatePublished - Aug 2002

Funding

FundersFunder number
National Institute of Neurological Disorders and StrokeR01NS039646

    Keywords

    • Cyclic ADP ribose
    • IP3
    • Miniature endplate potentials
    • Nicotinic acid adenine dinucleotide phosphate
    • Sphingosine 1-phosphate

    ASJC Scopus subject areas

    • Pharmacology

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