Reversible skeletal neuromuscular paralysis induced by different lysophospholipids.
Lysophosphatidylcholine rapidly paralyses the neuromuscular junction (NMJ), similarly to snake phospholipase A2 neurotoxins, implicating a lipid hemifusion-pore transition in neuroexocytosis. The mode and kinetics of NMJ paralysis of different lysophospholipids (lysoPLs) in high or low [Mg2+] was investigated. The following order of potency was found: lysophosphatidylcholine>lysophosphatidylethanolamine>lysophosphatidic acid>lysophosphatidylserine>lysophosphatidylglycerol. The latter two lysoPLs closely mimic the profile of paralysis caused by the toxins in high [Mg2+]. This paralysis is fully reversed by albumin washing. These findings provide novel insights on the mode of action of snake neurotoxins and qualify lysoPLs as novel agents to study neuroexocytosis.
Caccin
Paola
P
Dipartimento di Scienze Biomediche, Istituto C.N.R. Neuroscienze, Università di Padova, Viale G. Colombo n. 3, 35121 Padova, Italy.
Rigoni
Michela
M
Bisceglie
Alessandra
A
Rossetto
Ornella
O
Montecucco
Cesare
C
D000418:Albumins / Q000494:pharmacology; D000818:Animals; D003964:Diaphragm / Q000378:metabolism*; D005089:Exocytosis / Q000187:drug effects*; D008246:Lysophospholipids / Q000633:toxicity*; D008274:Magnesium / Q000494:pharmacology; D051379:Mice; D009469:Neuromuscular Junction / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity*; D009924:Organ Culture Techniques; D010243:Paralysis / Q000139:chemically induced*; D010741:Phospholipases A / Q000633:toxicity; D054467:Phospholipases A2; D010791:Phrenic Nerve / Q000378:metabolism*; D012910:Snake Venoms / Q000633:toxicity
D000418:Albumins; D008246:Lysophospholipids; D009498:Neurotoxins; D012910:Snake Venoms; D010741:Phospholipases A; D054467:Phospholipases A2; D008274:Magnesium