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Catecholamine accumulation and release in nervous tissue

Catecholamine accumulation and release in nervous tissue
Catecholamine accumulation and release in nervous tissue

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.

University of Southampton
Doggrell, Sheila Anne
Doggrell, Sheila Anne

Doggrell, Sheila Anne (1976) Catecholamine accumulation and release in nervous tissue. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

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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Published date: 1976

Identifiers

Local EPrints ID: 458698
URI: http://eprints.soton.ac.uk/id/eprint/458698
PURE UUID: 99cd2148-83d5-4cd5-9b12-59b02dca1726

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Date deposited: 04 Jul 2022 16:54
Last modified: 04 Jul 2022 16:54

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Author: Sheila Anne Doggrell

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