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Peptide mimetic of N-terminal ghrelin enhances ghrelin induced growth hormone secretion and c-Fos expression in mice.
Journal of Neuroendocrinology 2018 November 6
Orexigenic peptide ghrelin and its receptor have been extensively investigated as potential therapeutic targets, primarily due to their role in feeding initiation and growth hormone (GH) release. However, no specific ghrelin targeting anti-obesity or cachexia therapeutics are available for clinical use thus far and further efforts in this direction are warranted. Our objective was to find new peptide drug leads modulating ghrelin signal transduction. By targeting neutralizing antibodies against ghrelin with phage display libraries we aimed to identify peptides binding to the cognate receptor. Four synthetic peptides were selected and tested using calcium screening assays. The most effective competitive antagonist FSFLPPE was further tested in vivo. Administration of the peptide produced no significant effect on either food intake or GH release. Surprisingly, when co-administered with ghrelin the peptide significantly enhanced GH secretion and c-Fos expression. The evidence indicates that FSFLPPE might act as an ago-allosteric modulator. This article is protected by copyright. All rights reserved.
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