Maternal tobacco smoking and changes in amino acid uptake by human placental villi: induction of uptake systems, gammaglutamyltranspeptidase and membrane fluidity.
Maternal smoking depressed the active uptake of amino acids by human placentae and lowered their levels in the placenta and umbilical vein. During starvation of cells for amino acids, more amino acid carriers are induced and incorporated into the plasma membrane. A question arises whether there could be similar changes due to maternal smoking in the placental amino acid uptake carrier systems. Therefore, the characteristics of (a) the uptake of 2-amino[I-14C]-isobutyric acid (AIB) by isolated placental villi, (b) gammaglutamyltranspeptidase (GGTP), a critical enzyme of the gammaglutamyl cycle (GGC) for the uptake of amino acids in human placenta, and (c) lipid structural parameters (reciprocal of fluidity), by steady state fluorescence polarization of plasma membrane vesicles of microvilli (MV) and microsomal membranes (MM) of umbilical and chorionic plate arteries of placentae of smoking and non-smoking mothers were investigated. The above investigations gave the following results: (a) Washed placental villi of smokers exhibited higher capacity for AIB uptake than those of non-smokers. The higher uptake capacity was mainly due to increase in Vmax for AIB uptake in smokers. Km increased for placental AIB uptake in smokers. (b) Maternal smoking lowered GGTP activity of MV by decreasing its Vmax. Therefore, maternal smoking decreases the formation of gammaglutamyl-amino acid (GGAA) on the surface of trophoblast which are absorbed by the trophoblast. The degree of absorption of GGAA is considered as an inverse environmental signal for the cell to regulate amino acid transport systems. Maternal smoking seems to decrease the formation and absorption of GGAA and thereby induce the formation of new carriers for AIB uptake. (c) Maternal smoking increased the values for lipid structural order parameters and microviscosity of MV and induced tolerance against fluidization by ethyl alcohol in MM of umbilical and chorionic arteries. The alterations could increase Km for AIB uptake system and decrease the sensitivity of umbilical and chorionic arteries to vasoconstrictive substances like 5-hydroxytryptamine and catecholamine which are released by nicotine. All these changes tend to overcome the deficits produced in placental amino acid transport and satisfy the demands of the growing fetus for amino acids.
Sastry
B V
BV
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Horst
M A
MA
Naukam
R J
RJ
D000596:Amino Acids / Q000378:metabolism*; D000621:Aminoisobutyric Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D008560:Membrane Fluidity; D008563:Membrane Lipids / Q000378:metabolism; D008861:Microsomes / Q000201:enzymology; D011247:Pregnancy; D012907:Smoking / Q000378:metabolism*; D014327:Trophoblasts / Q000201:enzymology*; D014469:Umbilical Arteries / Q000378:metabolism; D014783:Viscosity; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D008563:Membrane Lipids; C100049:2-aminoisobutyric acid; D005723:gamma-Glutamyltransferase