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Title: The effects of lithium on adenosine triphosphatases and ion transport, with reference to affective illness
Author: Hesketh, John Edward
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1976
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The thesis describes investigations concerning the effects of lithium on ATPases and ion transport. Effects of potassium and lithium on sodium transport from blood to cerebrospinal fluid and brain were studied using a ventriculo-cisternal perfusion technique. The fast component of sodium entry into cerebrospinal fluid was correlated with the cisternal potassium concentration. This together with results showing the potassium-dependance of choroid plexus Na/K ATPase activity were interpreted as showing choroid plexus sodium transport to be sensitive to cerebrospinal fluid potassium concentration and to be due to Na/IC ATPase activity in the apical membranes of the plexuses. Effects of lithium on sodium transport were interpreted as a stimulation of the sodium pump when presented to the potassium-sensitive side and an inhibition when presented to the sodium-sensitive side. The effects of chronic lithium administration on ATPase activities were investigated in subcellular fractions prepared from rat cerebral cortex. Lithium was found to have no effect on synaptic plasma membrane Na/K ATPase activity but Mg ATPase specific activity was increased both in the membrane fraction and in mitochondria, after 21 and 7 days administration respectively. The changes in enzyme specific activity were not due to changes in fraction composition. Lithium administration for 21 days caused an increase in the concentration of homovanillic acid and 3,4-dihydroxyphenylacetic acid in the striatum. This was interpreted as showing an increased release and turnover of dopamine. ATPase activities were also studied in erythrocyte membrane preparations. Depressive patients were shown to have a reduced erythrocyte membrane Na/ATPase specific acitivity compared to controls. It is suggested that such a reduced enzyme activity could explain many of the previously observed derangements of sodium metabolism in depression. Lithium-treated patients showed increased specific activities of both Mg ATPase and Na/K ATPase in erythrocyte membranes; it is suggested that the increase in Na/K ATPase activity was due to recovery of the patients but that the increase in Mg ATPase activity was due to lithium itself. Lithium administration had no effect on erythrocyte membrane ATPase activities in the rat. It is concluded that chronic lithium administration affects the specific activities of certain Mg ATPases but not the Na/K ATPase. It is speculated that the changes in membrane ATPase activities reflect changes in actomyosin-like proteins which could lead to increases in the release of neurotransmitter in the brain.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available