Shah, Pir Mahroof; (1995) Isolation and study of histaminergic cells from the gastrointestinal tract of the human and other species. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

We have developed a method for the isolation of free mast cells from the colon and stomach of the human gastrointestinal (GI) tract and have investigated the histological and functional characteristics of these cells. In addition, we have compared the properties of mast cells isolated from normal tissue and from areas of active inflammation and have shown that the properties of the cells are altered in the disease state. On this basis, we have considered the possible role of the mast cells in the aetiology and pathogenesis of inflammatory bowel disease and gastroduodenal ulcer formation. In further studies, we investigated the effects of salicylates, H2-receptor antagonists, cytoprotectants and anti-inflammatory steroids on human colonic and gastric mast cells. Salicylates (sulphasalazine and its metabolites) had characteristic effects on histamine release from these mast cells. Sulphasalazine itself had no effect on histamine release induced by optimal amounts of an immunological stimulant but potentiated the secretion induced by suboptimal amounts of the antibody. In contrast sulphapyridine had no effect on histamine release but the active metabolite, 5-ASA, inhibited histamine release from all cell types. The action of this metabolite may then partially explain the therapeutic utility of sulphasalazine. A number of H2-receptor antagonists effectively inhibited histamine release from GI mast cells, suggesting that these compounds may have an additional action in the control of gastric acid secretion. The cytoprotectant misoprostol also inhibited histamine release, indicating that mast cell stabilization may contribute to therapeutic effect of the drug on the GI tract. The anti-inflammatory steroids betamethasone, hydrocortisone, methylprednisolone and prednisolone produced effective, time-dependent inhibition of histamine release from immunologically stimulated human GI mast cells. Such a response may account for the beneficial effects of these compounds in inflammatory bowel disease. We have developed a method for the isolation of enterochromaffin-like cells from the gastric mucosa of the rat and guinea-pig and have compared the properties of these cells with those of human GI mast cells. Finally, we have examined in detail the effects of acetylcholine and gastrin or pentagastrin, alone or in concert, on GI mast cells. A combination of the agonists was found to produce a marked release of histamine from the human cells, thus suggesting a new role for these cells in the control of gastric acid secretion.

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