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Title: The hormonal and pharmacological regulation of neuromuscular and myogenic human gastric activity
Author: Kouassi, Marie-Ange
ISNI:       0000 0004 9355 4714
Awarding Body: Queen Mary University of London
Current Institution: Queen Mary, University of London
Date of Award: 2020
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Although vomiting is well understood, a lack of an understanding of the pathophysiology of nausea remains. One potential explanation is that changes in the activity of the stomach induced by nauseogenic stimuli, may be transmitted through afferent nerves to activate the central nervous system. The role of gastric dysrhythmia during nausea is unknown, however, motilin receptor agonism is known to cause nausea. The aims of this thesis were to investigate the actions of nauseogenic stimuli in vitro to develop a model through which compounds with the ability to prevent irregular gastric rhythms can be identified. Human stomach specimens were collected from patients undergoing bariatric surgery after informed consent. Circular muscle strips were isolated from these samples, mounted in tissue baths and stimulated electrically to generate contractions. To isolate spontaneous mechanical activity, intrinsic neuronal function was inhibited and alterations in spontaneous mechanical activity were investigated in the presence of different pharmacological compounds. In the presence of motilin, neuronally evoked and spontaneous mechanical movements of the distal region of the stomach became irregular in amplitude and frequency. Compounds investigated for their ability to modulate ICC function, exerted minimal effects on spontaneous gastric activity and did not prevent gastric dysrhythmia. In the attempt to isolate single ICC from stomach using FACS, ICC with positive expression for both characteristic markers (c-Kit and Ano-1) could not be identified. Kit receptor expression of ICC was sensitive to enzymatic digestion so the cells were isolated using FACS based on their expression of the characteristic marker, Ano-1. Nausea may be experienced by individuals due to gastric dysrhythmia induced by several stimuli, for example, changes in plasma hormone levels or gastric distension. Compounds used to alter the spontaneous activity of the stomach exhibited limited effects perhaps due to the lack of specificity and selectivity in human tissue and positive feedback mechanisms that amplify ionic currents generated by ICC. Successful isolation of ICC may require the exclusion of FACS to improve the cell yield; favouring their recovery, survival and growth in culture.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available