Effects of some polymethylene bis(hydroxyethyl) dimethylammonium compounds on acetylcholine synthesis

British Journal of Pharmacology
B A Hemsworth

Abstract

1. The effects of some polymethylene bis(hydroxyethyl)dimethylammonium compounds have been studied on acetylcholine (ACh) synthesis and as substrates for choline acetyltransferase (ChAc).2. The decamethylene analogue (C(10)-dichol) inhibited ACh synthesis by mitochondrial (P(2)) fractions of guinea-pig cerebral cortex suspended in Tris buffer but had no effect on ACh synthesis by P(2) fractions when the membranes surrounding the ChAc enzyme were broken down by homogenization in Triton X-100.3. C(10)-Dichol was acetylated by ChAc almost to the same extent as choline. The initial rate of acetylation, at a concentration of 10(-3)M, was more rapid than for choline; however, the apparent Michaelis-Menten constant for C(10)-dichol was greater than the K(m) for choline, showing a loewr affinity for the ChAc enzyme.4. All the dicholine compounds were acetylated to some extent by ChAc and the rate of acetylation increased with an increase in the length of the methylene chain between the two quaternary nitrogen atoms in each dicholine molecule.5. The rate of acetylation of the dicholine compounds paralleled the activity of these analogues at the prejunctional site at the neuromuscular junction. The possibility is suggested that part of t...Continue Reading

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Citations

Jun 1, 1971·European Journal of Pharmacology·B A Hemsworth
Mar 1, 1979·Journal of Neurochemistry·J SollenbergB Sörbo
May 6, 2015·Molecular Pharmaceutics·Mathieu BerchelPaul-Alain Jaffrès
May 1, 1978·The Journal of Pharmacy and Pharmacology·B A Hemsworth, J M Cholakis
Apr 1, 1984·British Journal of Pharmacology·B A HemsworthG B Veitch
Jan 1, 1980·British Journal of Pharmacology·M DasJ R Vedasiromoni

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