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Beta‐bungarotoxin stimulates the synthesis and accumulation of acetylcholine in rat phrenic nerve diaphragm preparations.
Author(s) -
Gundersen C B,
Jenden D J,
Newton M W
Publication year - 1981
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1981.sp013535
Subject(s) - acetylcholine , chemistry , egta , bungarotoxin , phrenic nerve , phospholipase a2 , phospholipase , medicine , endocrinology , choline , neurotoxin , choline acetyltransferase , toxin , acetylcholine receptor , biochemistry , biology , calcium , respiratory system , receptor , enzyme , organic chemistry
1. The effects of beta‐bungarotoxin on acetylcholine (ACh) synthesis, tissue content and release have been studied in the rat diaphragm. A gas chromatographic mass spectrometric assay was used to measure ACh and choline. 2. Within 30 min, beta‐bungarotoxin (0.14 or 1.4 micrograms/ml.) caused a significant increase in tissue ACh content. This increase was apparent prior to the final inhibition by beta‐bungarotoxin of evoked (10 Hz) ACh release. 3. The toxin enhanced the incorporation of [2H4]Ch into [2H4]ACh in both resting and stimulated preparations. 4. Hemicholinium‐3 blocked the rise in diaphragm ACh normally produced by beta‐bungarotoxin. 5. Beta‐Bungarotoxin did not directly activate choline acetyltransferase in muscle homogenates. 6. The toxin‐induced rise in tissue ACh was largely absent in Ca2+‐free solutions which contained either EGTA (1 mM) or SrCl2 (2 or 10 mM). 7. Non‐neurotoxic phospholipases A2, fatty acids and the neurotoxic phospholipase A2, notexin, did not cause ACh accumulation in the diaphragm. 8. Beta‐Bungarotoxin did not stimulate ACh synthesis in denervated muscle. 9. The extra ACh which accumulated after beta‐bungarotoxin did not contribute to enhanced release by nerve impulses even when 4‐aminopyridine was added to the medium. High K+ solution and black widow spider venom were also ineffective in increasing output from toxin‐treated diaphragms relative to controls that had not been treated with beta‐bungarotoxin. 10. Prior injection of a rat with botulinum toxin prevented the accumulation of ACh due to beta‐bungarotoxin. Tubocurarine, however, did not antagonize beta‐bungarotoxin. 11. These data indicate that beta‐bungarotoxin has a unique capacity to inhibit ACh release and stimulate ACh synthesis in diaphragm nerve endings. The results are discussed in terms of a possible action of beta‐bungarotoxin to raise the level of ionized Ca in the nerve terminal cytosol.