Modulation of spontaneous transmitter release from the frog neuromuscular junction by interacting intracellular Ca(2+) stores: critical role for nicotinic acid-adenine dinucleotide phosphate (NAADP).
Nicotinic acid-adenine dinucleotide phosphate (NAADP) is a recently described potent intracellular Ca(2+)-mobilizing messenger active in a wide range of diverse cell types. In the present study, we have investigated the interaction of NAADP with other Ca(2+)-mobilizing messengers in the release of transmitter at the frog neuromuscular junction. We show, for the first time, that NAADP enhances neurosecretion in response to inositol 1,4,5-trisphosphate (IP(3)), cADP-ribose (cADPR) and sphingosine 1-phosphate (S1P), but not sphingosylphosphorylcholine. Thapsigargin was without effect on transmitter release in response to NAADP, but blocked the responses to subsequent application of IP(3), cADPR and S1P and their potentiation by NAADP. Asynchronous neurotransmitter release may therefore involve functional coupling of endoplasmic reticulum Ca(2+) stores with distinct Ca(2+) stores targeted by NAADP.
Department of Pharmacology, James H Quillen College of Medicine, East Tennessee State University, PO Box 70577, Johnson City, TN 37614, USA.
Eugen
E
Brailoiu
Sandip
S
Patel
Nae J
NJ
Dun
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D036563:Cyclic ADP-Ribose / Q000494:pharmacology; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D008246:Lysophospholipids; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009249:NADP / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011894:Rana pipiens; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014945:Wound Healing
D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D018377:Neurotransmitter Agents; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D036563:Cyclic ADP-Ribose; C060506:sphingosine 1-phosphate; D009249:NADP; C024376:NAADP; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D013110:Sphingosine; D002118:Calcium