Evidence for an involvement of membrane lipids in the control of neuronal nicotinic receptor function using bungarotoxin II-S1.
Previous work has shown that a toxin fraction, bungarotoxin (BGT) II-S1, isolated from Bungarus multicinctus venom could inhibit nicotinic receptor-mediated function. Experimental evidence suggested that this effect of the toxin might be due to a direct interaction of the toxin at the acetylcholine binding site and/or to its phospholipase activity. The toxin's enzymic activity has been further characterized; it has phospholipase activity of the A2 type with a Vmax of 12 pmol/min/ng protein and a Km of 300 microM. Phospholipases can produce their effects on a tissue through a variety of mechanisms including the disruption of important lipid protein bonds or the production of free fatty acids which interact with the tissue. To test for this latter possibility, various concentrations of fatty acid-free bovine serum albumin were added to the incubation medium. Fatty acid-free bovine serum albumin partially reversed the inhibition of carbachol-stimulated 1-[1,2-3H(N)]amino-4-guanidobutane ([3H]agmatine) uptake (used as a measure of ion flux) into the ganglion produced by BGT II-S1 (1.0 microM). In an attempt to determine which fatty acids might be responsible for this effect, various fatty acids were added to the incubation medium and their effect on nicotinic receptor-mediated [3H]agmatine uptake determined. Arachidonic acid decreased amine uptake by approximately 50% over the control carbachol-stimulated uptake; linoleic and oleic acid, on the other hand, did not significantly affect the response. This observation could imply that arachidonic acid is the fatty acid produced by the action of BGT II-S1 on the tissue to mediate the toxin's inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS)
D000200:Action Potentials / Q000187:drug effects; D000376:Agmatine; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D008563:Membrane Lipids / Q000502:physiology*; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects*
D001095:Arachidonic Acids; D002038:Bungarotoxins; D008041:Linoleic Acids; D008563:Membrane Lipids; D009829:Oleic Acids; D011978:Receptors, Nicotinic; D016718:Arachidonic Acid; D019301:Oleic Acid; D000376:Agmatine; D002217:Carbachol; D019787:Linoleic Acid; D010741:Phospholipases A