Doggrell, Sheila Anne (1976) Catecholamine accumulation and release in nervous tissue. University of Southampton, Doctoral Thesis.
Abstract
A study was made of the accumulation and release of sympathomimetic amines in nervous tissue. Most of the studies were carried out usingthe rat anococcygeus muscle, a preparation which had not been extensively studied previously.Tritiated (-)-noradrenaline, dopamine, (+)-adrenaline, and 2-amino, 6,7-dibydrov, 1,2,3,4-tetrahydronaphthalene'(ADTN) were rear3il accumulated by this tissue. After incubation in tritiated (-)-noradrenaline, the tritium is retained as noradrenaline.The ability of 21 sympathomimetic amines, angiotensin, 11 tricyclic antidepressant drugs, nomifensine and cocaine to inhibit (-)noradrenaline accumulation was investigated. The structure-activity relationships for inhibition are described. There was a good correlation between the ability of tricyclic antidepressant drugs to inhibit (-)-noradrenaline accumulation and potentiation of responses to (-)-noradrenaline except in the case of iprindole. The mechanism of action of iprindole and nomifensine is discussed.The ability of sympathomimetic amines to release (-)-noradrenaline was also studied.The responses to sympathomimetic amines were antagonised by phentolamine, an indication of the presence of oL-adrenoceptors. The mechanism of action of angiotensin is discussed. Sympathomimetic amines can either act directly on adrenoceptors or indirectly by releasing noradrenaline. The 3 established approaches toclassification of sympathomimetic amines were studied e.g. cocaine, reserpine or 6-hydroxydopamine pretreatment of animals. None of these approaches gave a satisfactory differentiation of direct and indirect actions. In addition 2 new approaches to classification were utilized; nortriptyline, to inhibit neuronal accumulation, and 6-hydroxydopamine preincubation of the muscle to deplete the noradrenaline stores. By these two methods it was possible to classify the 21 sympathomimetic amines utilized.
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