Extra- and Intracellular Sphingosylphosphorylcholine Promote Spontaneous Transmitter Release From Frog Motor Nerve Endings
Document Type
Article
Publication Date
6-1-2003
Description
Similar to phosphatidylinositol bisphosphate, sphingomyelin breakdown generates several lipids, including sphingosylphosphorylcholine (SPC), that are putative signaling molecules. The present study was undertaken to evaluate the involvement of SPC in transmitter release process. Intracellular recordings were made from isolated frog sciatic-sartorius nerve-muscle preparations, and the effects of SPC on neurosecretion in the form of miniature endplate potentials (MEPPs) were assessed. Extracellular application of SPC mixture (D,L-SPC) at 1, 10, and 25 μM increased the MEPP frequency by 68, 96, and 127%, respectively. D-erythro-SPC (dissolved in dimethyl sulfoxide but not coupled to bovine serum albumin), but not L-threo-SPC, was active extracellular; the former (at 10 μM) increased the MEPP frequency by 143%. D-erythro-SPC treatment did not significantly change the median amplitude or frequency-distribution of MEPPs. Intracellular delivery via liposomes, in which 10, 100, or 1000 μM SPC mixture was entrapped in liposomal aqueous phase, induced a concentration-dependent increase in MEPP frequency of 45, 91, and 100%, respectively. D-erythro-SPC and L-threo-SPC at the concentration of 100 μM increased the MEPP frequency by 117 and 67%, respectively, or 91 and 61%, respectively, when coupled to bovine serum albumin. Pretreatment with thapsigargin significantly reduced but did not abolish the effects of extracellular D-erythro-SPC (10 μM) or liposomes containing 100 μM D-erythro-SPC. Liposomes filled with 100 μM D-myo-inositol 1,4,5-trisphosphate (IP3) enhanced the MEPP frequency to the same magnitude as 100 μM D-erythro-SPC entrapped in liposomes. However, administration of 100 μM D-erythro-SPC and IP3 entrapped in the same liposomes enhanced the MEPP frequency by 70%, which was less than that produced by these two compounds alone. The result provides the first electrophysiological evidence that SPC can modulate transmitter release by an extra- or intracellular action at the frog motor nerve ending.
Citation Information
Brailoiu, Eugen; and Dun, Nae J.. 2003. Extra- and Intracellular Sphingosylphosphorylcholine Promote Spontaneous Transmitter Release From Frog Motor Nerve Endings. Molecular Pharmacology. Vol.63(6). 1430-1436. https://doi.org/10.1124/mol.63.6.1430 PMID: 12761354 ISSN: 0026-895X