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Int. J. Mol. Sci. 2017, 18(4), 859; doi:10.3390/ijms18040859

Clarifying the Ghrelin System’s Ability to Regulate Feeding Behaviours Despite Enigmatic Spatial Separation of the GHSR and Its Endogenous Ligand

Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON K1S 5B6, Canada
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Author to whom correspondence should be addressed.
Academic Editor: Suzanne L. Dickson
Received: 27 February 2017 / Revised: 4 April 2017 / Accepted: 11 April 2017 / Published: 19 April 2017
(This article belongs to the Special Issue Neurobiological Perspectives on Ghrelin)
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Abstract

Ghrelin is a hormone predominantly produced in and secreted from the stomach. Ghrelin is involved in many physiological processes including feeding, the stress response, and in modulating learning, memory and motivational processes. Ghrelin does this by binding to its receptor, the growth hormone secretagogue receptor (GHSR), a receptor found in relatively high concentrations in hypothalamic and mesolimbic brain regions. While the feeding and metabolic effects of ghrelin can be explained by the effects of this hormone on regions of the brain that have a more permeable blood brain barrier (BBB), ghrelin produced within the periphery demonstrates a limited ability to reach extrahypothalamic regions where GHSRs are expressed. Therefore, one of the most pressing unanswered questions plaguing ghrelin research is how GHSRs, distributed in brain regions protected by the BBB, are activated despite ghrelin’s predominant peripheral production and poor ability to transverse the BBB. This manuscript will describe how peripheral ghrelin activates central GHSRs to encourage feeding, and how central ghrelin synthesis and ghrelin independent activation of GHSRs may also contribute to the modulation of feeding behaviours. View Full-Text
Keywords: feeding; ghrelin; GHSR; blood brain barrier; vagal afferents; circumventricular organs; central ghrelin synthesis; GHSR heterodimerization; GHSR constitutive activity feeding; ghrelin; GHSR; blood brain barrier; vagal afferents; circumventricular organs; central ghrelin synthesis; GHSR heterodimerization; GHSR constitutive activity
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Edwards, A.; Abizaid, A. Clarifying the Ghrelin System’s Ability to Regulate Feeding Behaviours Despite Enigmatic Spatial Separation of the GHSR and Its Endogenous Ligand. Int. J. Mol. Sci. 2017, 18, 859.

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