Peptide receptors of the blood-brain barrier and substrate transport into the brain.
The BBB is a target for some peptide signals, as demonstrated by our group for arginine-vasopressin (AVP) and atriopeptin (ANP). Peptide molecules contacting the luminal surface of endothelial cells interact with specific high-affinity binding sites. The minimal simple diffusion of peptide molecules across the layer of endothelial cells which are connected by tight junctions is most probably without any significance under physiological conditions, although that question should be checked for brain regions like the olfactory bulb in which some leakiness of the BBB can be demonstrated. The AVP- and ANP-receptors at least partly localized at the luminal surface of the endothelial cells are heterogeneously distributed in the vessels of the brain. The number of AVP receptors is up-regulated by ligand deficiency, which induces furthermore a decrease in the receptor affinity. At physiological concentrations AVP and ANP do not affect the tightness of the BBB, but regulate the transcellular transfer of essential substances from blood to brain. AVP decreases the Km and Vmax of the transporter of large neutral amino acids, and ANP alters the water permeability of the endothelial cell layer. The phenomenon that the cells of the tight epithelium representing the BBB need information from blood-borne peptide signals for the regulation of intercompartmental transport processes seems to be only a special case of a general principle concerning tight epithelial cell layers which separate compartments containing fluids of different composition; amino acid transport across the intestine is regulated by specific peptides contacting that barrier, the casomorphins.
Ermisch
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Section of Biosciences, University of Leipzig, Germany.
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001692:Biological Transport; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D006728:Hormones / Q000032:analysis / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D011910:Rats, Brattleboro; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000378:metabolism*; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D017483:Receptors, Vasopressin
D006728:Hormones; D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor