Placenta transport

Transport. Transcobalamin II dehvers the absorbed vitamin 3 2 to cells and is the primary plasma vitamin B22-binding transport protein. It is found in plasma, spinal fluid, semen, and extracellular fluid. Many cells, including the bone marrow, reticulocytes, and the placenta, contain surface receptor sites for the transcobalamin II—cobalamin complex. 

Hydroxy vitamin D pools ia the blood and is transported on DBF to the kidney, where further hydroxylation takes place at C-1 or C-24 ia response to calcium levels. l-Hydroxylation occurs primarily ia the kidney mitochondria and is cataly2ed by a mixed-function monooxygenase with a specific cytochrome P-450 (52,179,180). 1 a- and 24-Hydroxylation of 25-hydroxycholecalciferol has also been shown to take place ia the placenta of pregnant mammals and ia bone cells, as well as ia the epidermis. Low phosphate levels also stimulate 1,25-dihydtoxycholecalciferol production, which ia turn stimulates intestinal calcium as well as phosphoms absorption. It also mobilizes these minerals from bone and decreases their kidney excretion. Together with PTH, calcitriol also stimulates renal reabsorption of the calcium and phosphoms by the proximal tubules (51,141,181—183). 

Epithelial calcium channel 1 (ECaCl), synonym TRJPV5, is a member ofthe TRP family of ion channels, implicated in vitamin D-dependent transcellular Ca2+ transport in epithelial cells ofthe kidney, placenta and the intestine. 

TRPV5 and TRPV6, also known as the epithelial Ca2+ channel or ECaC (TRPV5) and Ca2+transporter 1 or Ca2+ transporter-like (TRPV6), are the only two Ca2+-selective TRP channels identified so far. They may function in vitamin D-dependent transcellular transport of Ca2+in kidney, intestine and placenta. TRPV6 is also expressed in pancreatic acinar cells, and in prostate cancer, but not in healthy prostate or in benign prostate hyperplasia. 

Facilita GLUT1 ive bidirectionai transporters Brain, kidney, colon, placenta, erythrocyte Uptake of glucose... 

Steroid hormones are produced by the adrenal cortex, testes, ovaries, and placenta. Synthesized from cholesterol, these hormones are lipid soluble therefore, they cross cell membranes readily and bind to receptors found intracellularly. However, because their lipid solubility renders them insoluble in blood, these hormones are transported in the blood bound to proteins. Furthermore, steroid hormones are not typically preformed and stored for future use within the endocrine gland. Because they are lipid soluble, they could diffuse out of the cells and physiological regulation of their release would not be possible. Finally, steroid hormones are absorbed easily by the gastrointestinal tract and therefore may be administered orally. 

Recently, Prasad et al. cloned a mammalian Na+-dependent multivitamin transporter (SMVT) from rat placenta [305], This transporter is very highly expressed in intestine and transports pantothenate, biotin, and lipoate [305, 306]. Additionally, it has been suggested that there are other specific transport systems for more water-soluble vitamins. Takanaga et al. [307] demonstrated that nicotinic acid is absorbed by two independent active transport mechanisms from small intestine one is a proton cotransporter and the other an anion antiporter. These nicotinic acid related transporters are capable of taking up monocarboxylic acid-like drugs such as valproic acid, salicylic acid, and penicillins [5], Also, more water-soluble transporters were discovered as Huang and Swann [308] reported the possible occurrence of high-affinity riboflavin transporter(s) on the microvillous membrane. 

Griffiths, M., et al. Molecular cloning and characterization of a nitrobenzylfhioinosine-insensitive (ei) equilibrative nucleoside transporter from human placenta. Biochem. J. 1997, 328, 739-743. 

Kekuda, R., et al. Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta. J. Biol. Chem. 1998, 273, 15971-15979. 

Wu, X., et al. Structural and functional characteristics and tissue distribution pattern of rat OCTN1, an organic cation transporter, cloned from placenta. Biochim. Biophys. Acta 2000, 1466, 315-327. 

St-Pierre, M. V., etal. Characterization of an organic anion-transporting polypeptide (OATP-B) in human placenta. J. Clin. Endocrinol. Metab. 2002, 87, 1856-1863. 

Tamai et al. [30] cloned OATP-B from human brain and transporter mRNA has been detected in a number of other tissues including liver, lung, kidney, placenta, brain, heart and small intestine [26, 30]. Within the liver, OATP-B protein is local-... 

Within the OAT family, OAT4 is the only transporter expressed at appreciable levels in both the placenta and in the kidney [54]. The membrane localization of OAT4 within these tissues has not been examined. Steroid sulfates, and ochratoxinA are efficient transport substrates of OAT4, whereas PAH is weakly transported [54]. The functional importance of OAT4 in regulating placental permeability and renal drug elimination is currently unknown. 

Cha SH, Sekine T, Kusuhara H, Yu E, Kim JY, Kim DK et al. Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta. J Biol Chem 2000 ... 

Keywords Placenta Trophoblast Multidrug resistance Transport Cell culture... 

The human placenta expresses a number of nutrient and efflux transporters, as well as metabolic enzymes. Information about the placental function and regulation of these systems, and how they interact with the administered drug, can help to target them appropriately so as to limit fetal exposure to harmful substances. 

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