FIGURE 3.

Major blood-brain barrier transport systems. Endothelium: these include solute carrier-mediated transport (CMT), receptor-mediated transport (RMT), active efflux, and ion transport. CMT systems mediate transport of carbohydrates, amino acids, monocarboxylates, hormones, fatty acids, nucleotides, organic anions and cations, amines, choline, and vitamins with precise substrate specificity and directionality, as indicated. RMT systems transport proteins including transferrin, insulin, leptin, arginine vasopressin, amyloid-β (Aβ), glycosylated proteins, and apolipoproteins E (APOE) and J (APOJ). Active efflux includes ATP-binding cassette (ABC) transporters which transport xenobiotics, drugs, drug conjugates, and nucleosides from endothelium to blood, as indicated. Ion transport underlies the movement of Na⁺, K⁺, Cl⁻, HCO₃⁻, H⁺, and Ca²⁺ into and out of the endothelium via ATPases, uniporters, exchangers, and symporters, as indicated. Pericytes: presently, details about pericyte transporters’ cellular polarity and precise direction(s) of transport remain elusive. CMT systems transport carbohydrates, amino acids, carboxylates, organic anions and cations, and folate. RMT system transports Aβ, APOE, lipophilic molecules, and aminophospholipids. Ion transport of Na⁺, K⁺, Cl⁻, HCO₃⁻, H⁺, I⁻, and Ca²⁺ occurs via ATPases, uniporters, exchangers, and symporters, as indicated. All BBB transporters indicated here are validated with RNA-sequencing and/or proteomic analysis in the rodent brain. See the main text for a more detailed discussion.