DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Table 8–5
Characteristics of Plasma Membrane Transporters for Endogenous Catecholamines
TYPE OF SUBSTRATE REGION/CELL
TRANSPORTER SPECIFICITY TISSUE TYPE INHIBITORS
Neuronal
NET DA > NE > Epi All sympathetically Sympathetic nerves Desipramine
innervated tissue
Adrenal medulla Chromaffin cells Cocaine
Liver Capillary endothelial cells Nisoxetine
Placenta
Syncytiotrophoblast
DAT DA > NE > Epi Kidney Endothelium Cocaine
Stomach Parietal and Imazindol
endothelial cells
Pancreas
Pancreatic duct
Non-neuronal
OCT1 DA > Epi >> NE Liver Hepatocytes Isocyanines
Intestine Epithelial cells Corticosterone
Kidney (not human) Distal tubule
OCT2 DA >> NE > Epi Kidney Medullary proximal Isocyanines
and distal tubules Corticosterone
Brain
Glial cells of DA-rich
regions, some nonadrenergic
neurons
ENT (OCT 3) Epi >> NE > DA Liver Hepatocytes Isocyanines
Brain Glial cells, others Corticosterone
Heart Myocytes O-methyl-
Blood vessels Endothelial cells isoproterenol
Kidney
Cortex, proximal and
distal tubules
Placenta
Syncytiotrophoblasts
(basal membrane)
Retina
Photoreceptors, ganglion
amacrine cells
NET, norepinephrine transporter, originally known as uptake 1; DAT, dopamine transporter; ENT (OCT3), extraneuronal transporter, originally
known as uptake 2; OCT 1, OCT 2, organic cation transporters; Epi, epinephrine; NE, norepinephrine; DA, dopamine.
receptor agonist isoproterenol is not a substrate for this
system.
There are actually two neuronal membrane transporters
for catecholamines, the NE transporter (NET)
mentioned above and the DA transporter (DAT); their
characteristics are depicted in Table 8–5.
The NET is also present in the adrenal medulla, the liver,
and the placenta, whereas the DAT is present in the stomach, pancreas,
and kidney (Eisenhofer, 2001). NET and DAT are members
of an extended family of biogenic amine and amino acid neurotransmitter
transporters. Members share common structural motifs, particularly
the putative 12-transmembrane helices. These plasma
membrane transporters appear to have greater substrate specificity
than do vesicular transporters and are targets for specific drugs such
as cocaine (catecholamine transporters) and fluoxetine (serotonin
transporter).
Certain sympathomimetic drugs (e.g., ephedrine
and tyramine) produce some of their effects indirectly
by displacing NE from the nerve terminals to the extracellular
fluid, where it then acts at receptor sites of the
effector cells. The mechanisms by which these drugs
release NE from nerve endings are complex. All such
agents are substrates for NET. As a result of their transport
across the neuronal membrane and release into the
axoplasm, they make carrier available at the inner surface
of the membrane for the outward transport of NE