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Ghrelin analogs in food intake regulation
Pýchová, Miroslava ; Ryšlavá, Helena (advisor) ; Sofrová, Danuše (referee)
Ghrelin analogs in food intake regulation Ghrelin, to date the only known peripherally produced and centrally acting peptide that stimulates food intake, is mainly synthesized in the stomach and acts through growth- hormone-secretagogue receptor (GHS-R). In addition to its orexigenic effect, ghrelin stimulates growth hormone (GH) release, gastric motility and acid secretion. The diverse functions of ghrelin raise the possibility of its clinical application for GH deficiency, eating disorders, and gastrointestinal diseases. Ghrelin agonists could be a promising therapeutics in cachexia occurring at cancer or chronic inflammatory diseases. Octanoylation of Ser3 is crucial for preservation of ghrelin activity. In this study, biological properties (binding to GHS-R, food intake stimulation in mice) of full length and shorter ghrelin analogues with octanoic acid coupled to diaminopropionic acid (Dpr) replacing Ser3 or without octanoic acid were followed. This substitution resulted in a prolonged stability and orexigenic effect of above mentioned ghrelin analogues. Importance of N-terminal part of ghrelin and octanoylation peptide was also confirmed.
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