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NDPK activity and mast cell exoytosis

Martin, Matthew William; (1996) NDPK activity and mast cell exoytosis. Masters thesis (M.Phil), UCL (University College London). Green open access

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Regulated secretion is a physiological event by which chemical transmitters (neurotransmitters, hormones) and enzymes are released by a cell in response to an external stimulus. An approach to the investigation of regulated secretion is to use a model cell. In this study the mast cell has been used. The components of the pathway linking stimulus to secretion are located within the cell. Use of a bacterial lysin to make the cell membrane permeable allows soluble agents (drugs, nucleotides, ions, buffers) ready access to the cell interior. Thus the internal environment of the cell may be controlled facilitating investigation of the steps comprising the stimulus-secretion pathway. Guanine nucleotides are known to be involved at essential steps in the pathway. It is proposed that the enzyme nucleoside,5'-diphosphate kinase (NDPK) alters the phosphorylation state of guanine nucleotide in response to cellular stimulation and therefore has a modulatory' role in the control of secretion. An outline is provided of the involvement of mast cells in immune responses, allergic reactions and autoimmune disorders. Present understanding of the stimulus-secretion pathway is then reviewed. A detailed account of current models of the control mechanisms involved in regulated mast cell secretion is given. Distinction is made between the early events of signal transduction and later events that control the exocytotic machinery. In the context of signal transduction, brief consideration is given to the potential roles of phospholipases C and D. The major focus of this work is the possible role of NDPK in stimulated secretion. The suggested action of NDPK is in the phosphorylation of guanine nucleotide in response to a cell surface stimulus, facilitating activation of guanine nucleotide-binding proteins. Established ideas about the role of guanine nucleotide in secretion and the regulation of its phosphorylation state are presented. Evidence supporting the proposed role of NDPK is provided. The actions of the anti-asthmatic drug cromoglycate and a number of structurally related plant flavonoids on NDPK have been investigated. These findings are compared with the effects of cromoglycate and flavonoid compounds on permeabilised mast cells under conditions in which NDPK is expected to be involved at a critical step in stimulus-secretion coupling. Possible mechanisms by which polycationic mast cell secretagogues induce secretion are also discussed in the light of experimental evidence presented here.

Type: Thesis (Masters)
Qualification: M.Phil
Title: NDPK activity and mast cell exoytosis
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Nucleoside,5'-diphosphate kinase
URI: https://discovery.ucl.ac.uk/id/eprint/10106003
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