Shirley E. Freeman

Action of tricyclic anti-depressant drugs on central processes involving acetylcholine

Abstract Five trieyclic antidepressant drugs have been shown to be weak to moderate inhibitors of rat brain cholinesterase. Amitriptyline has been found to increase the ability of rat cerebral cortex slices to synthesize ACh, both in vitro and after chronic treatment with the drug. Rats injected with amitriptylamine did not show an increased synthetic ability until after 8 days treatment. An attempt has been made to correlate the rate of ACh synthesis with cell types in the cortical slices used. No clear cut effect was found. The tricycle antidepressants do not affect either the basal or the K + stimulated respiration of the cortex. In view of the known atropine-like activity of these compounds it is suggested that they may inhibit central muscarinic actions of ACh, whilst they stimulate nicotinic actions.

Effects of beta-receptor blocking drugs on cardiac metabolism

Abstract The effects of the three β-receptor blocking drugs pronethalol, propranolol and dichlorisopropyl-noradrenaline on changes in fat and carbohydrate metabolism induced by adrenaline were studied in isolated perfused rat and guinea-pig hearts. The actions of adrenaline on all aspects of metabolism examined were at least partially blocked by β-receptor blocking drugs. Therefore the β-receptor appears to be involved to a considerable extent in the acceleration of cardiac metabolism produced by adrenaline. There are differences in the action of β-receptor antagonists. Of the three drugs examined propranolol was the most effective antagonist of the actions of adrenaline on all aspects of metabolism except for the increase in glucose uptake, upon which its effects were minimal. There was a relationship between the amplitude of contraction in response to these agents and the amount of endogenous triglyceride utilized; this also held for the β-receptor antagonists and adrenaline.

The effect of high K+ solutions and fatty acid substrates on metabolic pathways in toad heart

Abstract 1. 1. The effects of high levels of external K+ and fatty acid substrates have been studied on the isolated ventricle of the toad, Bufo marinus . 2. 2. High K+ levels reduced ATP levels and increased levels of ADP and inorganic phosphate. 3. 3. High K + had marked effects on carbohydrate utilization and oxidation in winter toad hearts but had little effect on summer toad hearts. 4. 4. Contrary to findings on mammalian heart, toad ventricle glycogen stores were depleted by media containing octanoate or butyrate. This phenomenon, seen in summer toads, could be related to the synthesis of triglyceride and phospholipid.

THE ESTIMATION OF THE ACTIVITY OF ACETYLCHOLINESTERASE AND OTHER ESTERASES IN THE RAT BRAIN BY AN AMPEROMETRIC METHOD.

Abstract An amperometric method for the determination of acetylcholinesterase and other esterases in the rat brain has been described. Methyl mercuric iodide is used as a titrant against the — SH group available from the hydrolysis of the thioesters of choline. The end point is obtained when the current due to methyl mercuric iodide rises sharply. Kinetic constants determined by this method for crude rat brain extract and purified erythrocyte cholinesterase are presented.

Modifications of metabolism, ionic content and resting potential in toad heart by high potassium solutions

Abstract A study has been made of the effect of high levels of K+ in the external solution on the oxidative metabolism of the isolated ventricle of the toad heart. When the O2 uptake of ventricle slices was measured by Warburg methods, K+ was found to cause an increase in respiration. The increase was found at K+ levels equal or higher than 30 mM; between 50 and 100 mM it was constant regardless of the K+ level used. There was a concomitant increase in lactate formation. The increased respiration in high K+ solutions was less than is found in the sartorius muscle, also there was no optimal concentration of K+, as was found in the latter preparation. When the O2 uptake of the tissue was measured polarographically no increase in response to high K+ levels was found. This could not be related either to the presence of CO2 in the polarographic system, or to the accumulation of lactate in the small volume of Ringers solution used in the Warburg flask. Experiments using large Warburg flasks failed to show the response, which could, however, be shown when pyruvate was added to the polarographic system. The utilization of a fatty acid substrate by the heart led to an increase in O2 uptake; this was not further augmented by high K+ solutions. Pyruvate also led to an increased O2 usage; this was, however, augmented by high K+ solutions. It is suggested that fatty acid oxidation in the toad heart is insensitive to high K+ levels, whilst pyruvate oxidation is sensitive. On this evidence it appears that the stimulation of the enzyme complex responsible for the oxidative decarboxylation of pyruvic acid is at least partly the basis of the K+ effect. Ionic changes and changes in resting potential in response to high K+ were similar to those found in the toad sartorius.

An unknown phosphate compound in muscle

Abstract An unknown phosphate-containing compound has been isolated from the sartorius muscle of the toad. The compound was detected on paper chromatograms run to isolate the ademine nucleotides and creatine phosphate. Using solvent systems usually employed to separate ATP and ADP it was found to have an RF value identical to that of ADP, and consequently was routinely estimated with it. This finding accounts for the high values of ADP reported by us, taking account of the levels of creatine phosphate known to be present in muscle, and the activity of the creatine phosphoryltransferase system. The compound was found not to be a nucleotide, or a purine or pyrimidine derivative. Microanalysis showed it to contain C, N, H, orthophosphate and a large but constant proportion of non-combustible ash. Al was the principal metal contained in the ash. Evidence from infrared and ultraviolet spectra suggests that the compound contains an unsaturated heterocyclic ring. The Al may be present as a metal chelate with the phosphate moiety. The phosphate group of the compound failed to exchange with 32P-labelled orthophosphate under conditions when there was a substantial exchange of the other acid-soluble phosphate compounds of muscle. No information is available as to the possible biological function of the compound.