| Popis: |
This thesis initially proposes an hypothesis which relates clinical findings of abnormal body monovalent cation distribution and adrenocorti-costeroid secretion in subjects suffering affective disorders to the regulation of plasma membrane cation permeability. The hypothesis is partially examined by direct investigation of the sodium and potassium content and membrane magnesium-dependent adenosinetriphosphatase activities of erythrocytes from normal and affectively disordered human subjects. Thus, whilst erythrocyte sodium content remains normal, potassium content and monovalent cation-stimulated, magnesium-dependent adenosinetriphos-phatase activity are elevated in manic depression. Further investigations are concerned with determining the influence of adrenocorticosteroids upon these and related factors in rat skeletal muscle, kidney, erythrocytes and brain. They reveal that, whilst mono valent cation-stimulated, magnesium-dependent adenosinetriphosphatase activity remains uninfluenced by adrenocorticosteroid depletion in rat brain, it is reduced in skeletal muscle and kidney, and elevated in erythrocytes. Despite evidence for an associated significant decrease in the sodium content of rat erythrocytes, the rate of sodium efflux is reduced, and the activity of another membrane-associated enzyme (acetylcholinesterase) remains uninfluenced. Although the dietary administration of isotonic sodium chloride solution is shown to counteract a number of the effects of adreno corticosteroid depletion upon rat tissues in a manner which suggests that renal sodium reabsorption is the principal hormone-sensitive target process, certain results obtained in skeletal muscle and erythrocyte studies are interpreted in terms of an extra-renal regulatory influence of adrenocorti costeroids upon plasma membrane characteristics. Experimental observations are discussed throughout in association with those established by previous workers, and in connexion with the extent to which adrenocorticosteroidal control of monovalent cation distribution may be implicated in the aetiology of manic-depression. This finally leads to a reconsideration of the clinical evidence for abnormal monovalent cation distribution in mania and depression, and of the hypothesis initially proposed. |
