Transendothelial Transport and Its Role in Therapeutics

Table 4

Major neurotransmitter transporters occur at blood brain barrier.

Neurotransmitters	Transporter/mechanism	Location	Influx or efflux/function	References
Neurotransmitters	Diffusion	Membrane of presynaptic and postsynaptic neuron fiber	Influx	[86]
Choline	Carrier-mediated process	Membrane of presynaptic and postsynaptic neuron fiber	Influx and efflux regulate the formation of acetylcholine in the central nervous system.	[87]
Acetylcholine	Facilitated diffusion, saturable glycoproteins (Pgp) transport system	Neuronal circuits of brain, membrane of presynaptic, and postsynaptic neuron fiber	Influx, Synaptic transmission, occurs in peripheral nervous system.	[86, 88–90]
Glycine	Receptor mediated	Membrane receptors	Makes the postsynaptic membrane more permeable to Cl-ions.
Aspartate	Aspartate ion channel	Membrane receptors
Glutamate	Glutamate chloride-independent membrane transport system	Membrane receptors
Glutamate/asparate	ATP-driven Na^+-K^+-ase	Membrane receptors
Biogenic amines, norepinephrine	Norepinephrine transporter, uptake1 and uptake2 carrier-mediated transporters, Net (Slc6a2), Dat (Slc6a3), and Sert (Slc6a4)	Norepinephrine	Norepinephrine transporter Alzheimer's disease and attention deficient hyperactivity disorder	[68, 92, 93]; [94–96]; [97]
Melatonin		Membrane receptors	Melatonin receptors in the area postrema located outside the blood-brain barrier	[98, 99]
Peptides		Membrane receptors		[100]
Cholecystokinin-1 receptor agonist	Cholecystokinin-1 receptor agonist	Membrane receptors		[101, 102]
GI hormone		Membrane receptors		[103, 104]
Insulin, transferrin, insulin-like growth factors and vasopressin	Receptor-mediated transcytosis	Membrane receptors		[105]
Serotonin		Serotonin
GABA (GAT2, BGT1)	Amino acid transporter	GABA	GABA imposes inhibitory effects on the brain neurons that show protective role during hypoxia or ischemia, active transport into the astrocyte glial cells
Nucleoside transporters
Equilibrative; nucleoside transporters (ENTes & ENTei)	Nucleoside transporters	Nucleoside	Purine and pyrimidine nucleosides, purine, and pyrimidine nucleosides
Ion transporters
Na/K-ATPase	Active transport	Potassium	Nerve conduction
Ca-ATPase	Active transport	Calcium	Bone marrow
Sodium	Active transport	Sodium	Nerve conduction
Potassium, chloride	Active transport	Potassium/chloride cotransporter	Nerve conduction
ATP-binding cassette (ABC) transporters
P-glycoprotein (P-gp) multidrug resistance transporter; (mouse; Mdr1a [Mdr3], Mdr1a [Mdr3],; Mdr1b [Mdr1], and; Mdr2; human MDR1 & 2)	Active transport	Organic, hydrophobic, and amphipathic cations: -adrenergic blockers, anthracyclines,; cyclosporine A, digoxin, etoposide, glucocorticoids, loperamide,; morphine, phenytoin, vecuronium, verapamil, and vinca alkaloids	Inhibition of drug transport
Multidrug resistance associated protein (MRP1)	Active transport	Amphipathic anions and glutathione, glucuronide and sulfate conjugates: benzylpenicillin, doxorubicin, etoposide,; methotrexate, vinblastine, and; vincristine	Efflux
MRP2 (c-MOAT)	Active transport	Organic anions	Efflux
MRP3 (MOAT-D)	Active transport	Methotrexate, anionic conjugates	Efflux
MRP4 (MOATB)	Active transport	Nucleoside-based antivirals	Efflux
MRP5 (MOAT-C)	Active transport	Cyclic nucleotides, glutathione conjugates, and organic anions	Efflux
MRP6 (MOAT-E)	Active transport	Peptides	Efflux
Breast cancer resistance protein BCRP)	Active transport	Similar to P-gp substrates; camptothecin derivatives, daunorubicin, doxorubicin,; mitoxantrone, and topotecan	Efflux
OCT1-3,	Active transport	Monoamine neurotransmitters, cationic neurotoxins, amantadine, memantine, desipramine, dopamine, and serotonin	Influx and efflux
OCTN1	Active transport	Antiarrhythmic drugs, tetraethylammonium verapamil	Influx and efflux
OCTN2		-lactam antibiotics, L-carnitine, and tetraethylammonium	Influx and efflux
Organic ion transporting polypeptide 1 (oatp1, OATP1)	Active transport	Bulky organic cations, glucuronide conjugates, steroid hormones, estrone sulfate, indinavir, nelfinavir, opioid agonists, and ouabain	Influx and efflux
Oatp2, OATP2	Active transport	Amphipathic anions: bile acids, cholate, digoxin, estrogen conjugates, opioid agonists, and ouabain, taurocholate; dehydroepiandrosterone sulfate and; estrone-1-sulfate efflux; 26-enkephalin; 3,5,3-triiodo-L-thyronine	Influx and efflux
Oatp3	Active transport	Digoxin, 26-enkephalin, fexofenadine 3,5,3-triiodo-L-thyronine	Influx and efflux
BBB-specific anion transporter type 1 (Bsat1,; oatp14)	Active transport	T4	Influx and efflux
OATP-A, OAT1, OAT3	Active transport	Amphipathic anions, bile acids, deltorphin; II, estrone-1-sulfate, fexofenadine,; opioid peptides, and benzylpenicillin Cimetidine, dehydroepiandrosterone sulfate, estrone sulfate,; indoxyl sulfate, and PAH	Influx and efflux