Regulation of enzymes responsible for neurotransmitter synthesis and degradation in cultured rat sympathetic neurons. III. Effects of sodium butyrate.
The effects of Na butyrate on the differentiation of newborn rat sympathetic neurons in primary cultures have been studied. Butyrate did not affect the long-term survival of these neurons in the presence of optimal concentrations of nerve growth factor, but decreased in a dose-dependent manner their protein content. In the range, 0.5-20 mM, butyrate did not modify the specific activity of lactate dehydrogenase in these cultures. Choline acetyltransferase activity developed at a 4.5- to 12-fold higher rate in cultures grown with 1-5 mM butyrate than in its absence. Concomitantly, tyrosine hydroxylase, dopa decarboxylase, dopamine-beta-hydroxylase, and acetylcholinesterase were depressed in cultures grown with butyrate. The deficit in acetylcholinesterase total activity was accompanied by an inhibition of the development of the asymmetric 16 S form of the enzyme. The deficit in tyrosine hydroxylase activity did not result from either a modification of the app Km for the enzyme's cofactor or a modification of its state of cAMP-dependent phosphorylation, but from a decrease in the number of immunoprecipitable enzyme molecules. A similar result was obtained with acetylcholinesterase. Butyrate thus reproduced in a qualitative manner the effects of a macromolecular factor purified from muscle conditioned medium on these neurons (J. P. Swerts, A. LeVan Thaï, A. Vigny, and M. J. Weber (1983) Dev. Biol. 100, 1-11; J. P. Swerts, Le Van Thai, and M. J. Weber (1984) 103, 230-234), raising the hypothesis of a common pathway in the regulation of neurotransmitter phenotype by these two agents.
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004296:Dopa Decarboxylase / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D013564:Sympathetic Nervous System / Q000201:enzymology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002087:Butyrates; D007527:Isoenzymes; D018377:Neurotransmitter Agents; D020148:Butyric Acid; D007770:L-Lactate Dehydrogenase; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D004296:Dopa Decarboxylase