Receptor-mediated transporters blood-brain barrier

Methyldopa (dopa = dihydroxy-phenylalanine), as an amino acid, is transported across the blood-brain barrier, decarboxylated in the brain to a-methyldopamine, and then hydroxylat-ed to a-methyl-NE The decarboxylation of methyldopa competes for a portion of the available enzymatic activity, so that the rate of conversion of L-dopa to NE (via dopamine) is decreased. The false transmitter a-methyl-NE can be stored however, unlike the endogenous mediator, it has a higher affinity for a2- than for ai-receptors and therefore produces effects similar to those of clonidine. The same events take place in peripheral adrenergic neurons. 

Banks, W.A., et al. 2002. Leptin transport across the blood-brain barrier of the Koletsky rat is not mediated by a product of the leptin receptor gene. Brain Res 950 130. 

TfR-mediated endocytosis is a well-known uptake system Tf binds one or two Fe atoms, but only diferric Tf (Fe2Tf) has a high affinity for TfR to be taken up by the receptor-mediated endocytosis. This system uses a mobilization pathway that involves endosomal acidification, reduction of ferric Fe, and ferrous Fe transport [8]. Recently, it was clarified that divalent cation/ metal ion transporter (DCT1) or Nramp2 involves iron transport from the endosome to the cytosol [9, 10]. Al resembles Fe in chemical characteristics ionic radius, charge density, and coordination number [11]. Therefore, Al binds with Tf to form di—Al—Tf. Al bound to Tf even passes through the blood-brain barrier to enter the neuronal cells via Tf receptor-mediated endocytosis [12]. 

Urayama A, Grubb JH, Sly WS, Banks WA (2004) DevelopmentaUy regulated mannose 6- phosphate receptor-mediated transport of a lysosomal enzyme across the blood-brain barrier. Proc Natl Acad Sci USA 101 12663. 

ROLE OF TRANSPORT PROCESSES AT THE BLOOD-BRAIN BARRIER RECEPTOR-MEDIATED TRANSPORT OF DRUGS... 

Figure 2 Schematic illustration of the (transport) properties of the blood-brain barrier. Shown is the influence of astrocyte endfeet at the brain capillary endothelial cell. This cell has narrow tight junctions, low pinocytotic activity, many mitochondria, and luminal anionic sites that hinder the transport of negatively charged compounds. Passive hydrophilic transport occurs via paracellular diffusion (tight junctions), whereas passive lipophilic transport is a transcytotic process. Adsorptive-, receptor-, and carrier-mediated transport has been indicated. The metabolic properties of the BBB are illustrated by the various enzymes at the BBB [from (157), with permission].

Nanospheres for oral delivery Encapsulating the bioactive molecules prevents enzymatic degradation of drug which makes it an apt vehicle for oral delivery. Nanospheres for drug delivery in the brain Capability of targeting specific receptor-mediated transport system in the blood—brain barrier (BBB) makes nanospheres an ideal choice for drug delivery in the brain. For example, Polysorbate 80/LDL is capable of delivery to the brain. 

W.M. Pardridge, Receptor-mediated peptide transport through the blood-brain barrier. Endocrine Rev 7 31A-330 (1986). 

---