In general, peripherally synthesized peptides are not readily available to cross the BBB or directly impact the functioning of CNS. However, the growing knowledge about BBB physiology and its (im)permeability, as well as about physiology of peptides, especially ones from the GI in the context of gut-brain axis, brings some interesting questions. I've seen ghrelin was shown to be one of the GI peptides that readily crosses the BBB and binds to its CNS receptors. Are there any other peptides that cross the BBB and bind to respective receptors in such a manner?
The attached papers that discuss some matters mentioned in the question are:
The blood-brain barrier: connecting the gut and the brain. Banks WA. Regul Pept. 2008 Aug 7;149(1-3):11-4
Ghrelin signalling and obesity: at the interface of stress, mood and food reward. Schellekens H, Finger BC, Dinan TG, Cryan JF. Pharmacol Ther. 2012 Sep;135(3):316-26.
Insulin-like growth factor-1 (IGF-1) is also found to cross the BBB. Though its also found to be produced endogenously by the neuronal cell, there are papers that have found that IGF-1 produced peripherally crosses the BBB.
Article Interactions of IGF-1 with the Blood-Brain Barrier in vivo and in situ
Policationic peptides such as defensins crotamine can induce endocytosis whereas the equali charged protamin makes heteropolymers at the basement membrane and do not cross BBB. Please go to my papers avaiable here in RG. Gyroxin a glycoprotein negatively polarized brought breakdown of the BBB by inducing drastic conformational changes in the basement membrane and thus the free molecules could cross.
The results showed ad hoc behaviour instead of a credible hypothesis
Maybe the following papers will help you:
1. Banks WA. Peptides and the blood–brain barrier. Peptides. 2015;72:16-19. doi:10.1016/j.peptides.2015.03.010.
2. Banks WA. Brain Meets Body: The Blood-Brain Barrier as an Endocrine Interface. Endocrinology. 2012;153(9):4111-4119. doi:10.1210/en.2012-1435.
3. Maryanovich AT, Kormilets DY, Polyanovsky AD. Regulatory Peptides: Exchange across the Blood-Brain Barrier. J Psychol Brain Stud. 2017, 1:5.
4. Itzik Cooper,Keren Sasson, Vivian I. Teichberg, Michal Schnaider-Beeri,Mati Fridkin,and Yoram ShechterPeptide Derived from HIV-1 TAT Protein Destabilizes a Monolayer of Endothelial Cells in an in Vitro Model of the Blood-Brain Barrier and Allows Permeation of High Molecular Weight Proteins. THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 287, NO. 53, pp. 44676 –44683, December 28, 2012
5. W. M. Pardridge .Transport of Nutrients and Hormones through the Blood-Brain Barrier . Diabetologia (1981) 20:246-254
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