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Sphingosine 1‐phosphate enhances spontaneous transmitter release at the frog neuromuscular junction
Author(s) -
Brailoiu Eugen,
Cooper Robin L,
Dun Nae J
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704839
Subject(s) - neuromuscular junction , extracellular , biophysics , intracellular , neuromuscular transmission , acetylcholine , liposome , grenouille , chemistry , biology , anatomy , neuroscience , endocrinology , biochemistry , salientia , xenopus , gene
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 μ M ) 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. British Journal of Pharmacology (2002) 136 , 1093–1097. doi: 10.1038/sj.bjp.0704839