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Some studies on histamine release from mast cells stimulated with somatostatin and other secretagogues

Kassessinoff, Tatiana Amanda; (1991) Some studies on histamine release from mast cells stimulated with somatostatin and other secretagogues. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

A variety of polybasic compounds and neuropeptides release histamine from rat serosal mast cells. In the present study, the effect of somatostatin on different mast cells was examined in detail. In this way, it was hoped to elucidate further the mechanisms involved in the activation of mast cells by polyamines and neuropeptides and the possible importance of the latter effect in allergy and inflammation. Somatostatin was shown to be an effective histamine liberator from rat peritoneal mast cells. The process was non-cytotoxic and resembled that evoked by other polybasic agents such as compound 48/80 and substance P in being extremely rapid, independent of extracellular calcium ions and unaffected by added phospholipids. The release was not inhibited by antagonists of the dextran receptor and was independent of cell-fixed antibody. However, secretion was selectively blocked by antagonists of the purported polyamine receptor, benzylammonium chloride (BAC) and benzyl dimethyltetradecyl ammonium chloride (BDTA), and by the C-terminal octapeptide fragment of substance P4 SP4-11. Crossdesensitisation was observed between somatostatin and other polyamines but not between the neuropeptide and immunologic stimuli. The effect of somatostatin was species and tissue specific. Rat pleural mast cells responded in similar fashion to those from the peritoneum while the latter cells from the hamster and mouse were considerably less reactive. Tissue mast cells of the rat showed graded responsivity while such cells from the guinea pig, the pig and the human were essentially unreactive. Where studied, the relative responsiveness of different mast cells was mirrored by fluorescence binding studies. Varying concentrations of somatostatin did not strikingly modulate immunologic or pharmacologic histamine release from human basophils or murine mast cells. The precise conditions required for BDTA to act as a selective antagonist of polyamine-induced release were established and detailed studies showed the antagonism to be surmountable. The release induced by somatostatin and other polyamines was inhibited by treatment of the cells with neuraminidase and by pertussis toxin, suggesting that sialic acid may be involved in the binding of such agonists to the cell membrane and that a G-protein(s) may be involved in the transduction mechanism.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Some studies on histamine release from mast cells stimulated with somatostatin and other secretagogues
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; Serosal mast cells
URI: https://discovery.ucl.ac.uk/id/eprint/10114192
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