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Inhibition of Phosphorylation of Synapsin I and Other Synaptosomal Proteins by β‐Bungarotoxin, a Phospholipase A 2 Neurotoxin
Author(s) -
Ueno Eiko,
Rosenberg Philip
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb10091.x
Subject(s) - phosphorylation , synapsin i , neurotoxin , phospholipase a2 , phosphatase , biochemistry , bungarotoxin , chemistry , veratridine , biology , enzyme , synaptic vesicle , sodium channel , nicotinic agonist , sodium , vesicle , receptor , organic chemistry , membrane
Some snake venom neurotoxins, such as β‐bungarotoxin (β‐BuTX), which possess relatively low phospholipase A 2 (PLA 2 ) activity, act presynaptically to alter acetylcholine (ACh) release both in the periphery and in the CNS. In investigating the mechanism of this action, we found that β‐BuTX (5 and 15 n M ) inhibited phosphorylation, in both resting and depolarized synaptosomes, of a wide range of proteins, including synapsin I. Naja naja atra PLA 2 , which has higher PLA 2 activity, also inhibited phosphorylation but was less potent than β‐BuTX. At 1 n M , β‐BuTX and N. n. atra PLA 2 inhibited phosphorylation of synapsin I only in depolarized synaptosomes. Synaptosomal ATP levels were not affected by 5 or 15 n M β‐BuTX or by 5 n M N. n. atra PLA 2 . Limited proteolysis, using Staphylococcus aureus V‐8 protease, indicated that β‐BuTX inhibited phosphorylation of synapsin I in both the head and the tail regions. The inhibition of phosphorylation was not antagonized by nordihydroguaiaretic acid or indomethacin, suggesting that arachidonic acid derivatives do not mediate this inhibition. Furthermore, inhibition of phosphorylation by β‐BuTX and N. n. atra PLA 2 was not altered in the presence of the phosphatase inhibitor okadaic acid, suggesting that stimulation of phosphatase activity is not responsible for this inhibition. Inhibition of protein phosphorylation by PLA 2 neurotoxins and enzymes may be associated with an inhibition of ACh release.