Sphingosine 1-phosphate enhances spontaneous transmitter release at the frog neuromuscular junction.
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 micro 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.
Brailoiu
Eugen
E
Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, PO Box 70577, Johnson City 37614, USA.
Cooper
Robin L
RL
Dun
Nae J
NJ
D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology; D005110:Extracellular Space; D066298:In Vitro Techniques; D007424:Intracellular Fluid; D008081:Liposomes; D008246:Lysophospholipids; D009045:Motor Endplate / Q000187:drug effects / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology*; D011894:Rana pipiens; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009435:Synaptic Transmission
D008081:Liposomes; D008246:Lysophospholipids; D018377:Neurotransmitter Agents; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; C060506:sphingosine 1-phosphate; D013110:Sphingosine