The action of notexin from tiger snake venom (Notechis scutatus scutatus) on acetylcholine release and compartmentation in synaptosomes from electric organ of Torpedo marmorata.
At rest, in the presence of calcium, notexin induced a rapid and concentration-dependent leakage of acetylcholine from nerve endings. In the presence of 20 nM notexin (5 min), synaptosomes were well-preserved structurally and they responded to addition of A23187 ionophore by a normal calcium-dependent acetylcholine release. When stimulated by high-K+ depolarization, evoked acetylcholine release was increased when notexin was present. These findings demonstrate that notexin (up to 100 nM) does not inhibit the acetylcholine release process itself. Further studies on intracellular acetylcholine compartmentation showed that, in the presence of calcium, nm concentrations of notexin were able to mobilize vesicular acetylcholine, the amount of which strongly decreased and fed the cytoplasmic compartment leading to an important redistribution of the neurotransmitter. Other metabolic studies under notexin confirmed the inhibition of the synaptosomal membrane choline transport, but failed to elicit changes in the choline acetyltransferase activity. In order to distinguish between the phospholipase A2 activity of notexin and its neurotoxic effects, we compared effects of notexin to those obtained with a non-neurotoxic pancreatic phospholipase A2. The latter exhibits similar effects but at a higher range of concentration than notexin.
Mollier
P
P
Service de Biochimie, Centre d'Etudes Nucléaires de Saclay, Gif-sur-Yvette, France.
Brochier
G
G
Morot Gaudry-Talarmain
Y
Y
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002794:Choline / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000032:analysis; D004546:Elapid Venoms / Q000494:pharmacology*; D004557:Electric Organ / Q000737:chemistry*; D009498:Neurotoxins / Q000494:pharmacology*; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D011189:Potassium Chloride / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D014101:Torpedo / Q000378:metabolism*
D004546:Elapid Venoms; D009498:Neurotoxins; C005082:notexin; D011189:Potassium Chloride; D002795:Choline O-Acetyltransferase; D010741:Phospholipases A; D054467:Phospholipases A2; D002794:Choline; D000109:Acetylcholine