Placental toxicology: tobacco smoke, abused drugs, multiple chemical interactions, and placental function

1991 ◽  
Vol 3 (4) ◽  
pp. 355 ◽  
Author(s):  
BV Sastry
Keyword(s):  
Amino Acid ◽  
Amino Acid Transport ◽  
Drugs Of Abuse ◽  
Amino Acid Uptake ◽  
Transport Systems ◽  
Acid Uptake ◽  
Acid Transport ◽  
Ach Release ◽  
Placental Blood ◽  
Abused Drugs

There are increasing numbers of reports on the tobacco smoking and ingestion of abused drugs (e.g. morphine, cocaine) by pregnant women and the effects of the substances on the developing fetus and newborn infant. The passage of drugs and chemicals from the mother to the fetus is influenced by the placental transport and metabolism of the substances. Further, these drugs and chemicals affect the nutrient transport systems in the placenta. The three major drugs of abuse-nicotine, morphine and cocaine-depress both active amino-acid uptake by human placental villi and transplacental amino-acid transport by reason of the drugs' influence on placental cholinergic and opiate systems. Part of this depression (10-16%) is not reversible. Nicotine blocks the cholinergic receptor and thus blocks acetylcholine (ACh)-facilitated amino-acid transport. Morphine stimulates opiate kappa receptors and depresses ACh release. Cocaine blocks Ca2+ influx and thus blocks ACh release. ACh causes dilation of blood vessels and maintains placental blood flow by the activation of endothelial muscarinic receptors. By interfering with ACh release and placental blood flow, the three drugs of abuse may depress the diffusion of amino acids and other nutrients from the trophoblast into the placental circulation. Three regulatory systems are delineated for amino-acid uptake by the placenta: placental ACh, phospholipid N-methyltransferase, and the gammaglutamyl cycle. These systems operate in concert with one another and are dependent on cellular formation of adenosine 5'-triphosphate (ATP). Placental hypoxia induced by carbon monoxide and other tobacco gases depresses the energy-dependent processes and thus the ATP levels of placental cells. Maternal tobacco smoking and drug abuse cause placental insufficiencies for amino-acid transport, which may partially explain the fetal intrauterine growth retardation caused by these substances. Part of the amino-acid deficits may be compensated for by the induction of new amino-acid transport systems. Specific receptors or drug-binding proteins for the three drugs of abuse are present in the placenta. A DNA adduct selective for maternal smoking has been demonstrated in the placenta. DNA adducts selective for cocaine, morphine and other environmental chemicals have yet to be demonstrated ins the placenta.

In vivo muscle amino acid transport involves two distinct processes

2004 ◽  
Vol 287 (1) ◽  
pp. E136-E141 ◽  
Author(s):  
Sharon Miller ◽  
David Chinkes ◽  
David A. MacLean ◽  
Dennis Gore ◽  
Robert R. Wolfe
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Transport ◽  
Interstitial Fluid ◽  
Muscle Blood Flow ◽  
Amino Acid Uptake ◽  
Transport Systems ◽  
Acid Uptake ◽  
Acid Transport ◽  
Rate Limiting

We have tested the hypothesis that transit through the interstitial fluid, rather than across cell membranes, is rate limiting for amino acid uptake from blood into muscle in human subjects. To quantify muscle transmembrane transport of naturally occurring amino acids, we developed a novel 4-pool model that distinguishes between the interstitial and intracellular fluid compartments. Transport kinetics of phenylalanine, leucine, lysine, and alanine were quantified using tracers labeled with stable isotopes. The results indicate that interstitial fluid is a functional compartment insofar as amino acid kinetics are concerned. In the case of leucine and alanine, transit between blood and interstitial fluid was potentially rate limiting for muscle amino acid uptake and release in the postabsorptive state. For example, in the case of leucine, the rate of transport between blood and interstitial fluid compared with the corresponding rate between interstitial fluid and muscle was 247 ± 36 vs. 610 ± 95 nmol·min−1·100 ml leg−1, respectively ( P < 0.05). Our results are consistent with the process of diffusion governing transit from blood to interstitial fluid without selectivity, and of specific amino acid transport systems with varying degrees of efficiency governing transit from interstitial fluid to muscle. These results imply that changes in factors that affect the transit of amino acids from blood through interstitial fluid, such as muscle blood flow or edema, could play a major role in controlling the rate of muscle amino acid uptake.

scholarly journals Evidence against the participation of the γ-glutamyltransferase-γ-glutamylcylclotransferase pathway in amino acid transport by rabbit erythrocytes

1975 ◽  
Vol 152 (3) ◽  
pp. 713-715 ◽  
Author(s):  
J D Young ◽  
J C Ellory ◽  
P C Wright
Keyword(s):  
Amino Acid ◽  
Amino Acid Transport ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Acid Transport

The GSH concentration of rabbit erythrocytes was monitored under conditions of large net transport of alanine, phenylalane and lysine in the absence of glucose. In no case was there an appreciable alteration in GSH concentration during amino acid uptake. It is suggested that the γ-glutamyltransferase-γ-glutamylcyclotransferase pathway does not participate in amino acid transport by these cells.

Active Transport of α-Aminoisobutyric Acid by the Isolated Midgut of Hyalophora Cecropia

1972 ◽  
Vol 56 (1) ◽  
pp. 167-172
Author(s):  
SIGNE NEDERGAARD
Keyword(s):  
Amino Acid ◽  
Active Transport ◽  
Opposite Direction ◽  
Amino Acid Transport ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Acid Transport ◽  
Active Process ◽  
Aminoisobutyric Acid ◽  
Amino Acid Flux

1. The α-aminoisobutyric acid flux from lumen to blood of the isolated Cecropia midgut is around 17 µmole/h, while the amino acid flux in the opposite direction is on average 0.3 µmole/h. 2. The amino acid uptake is inhibited by lack of oxygen. It is suggested that the amino acid transport from lumen to blood is an active process. 3. The amino acid uptake is inhibited by short-circuiting the midgut potential, indicating that there is no direct correlation between the active transport of potassium and the uptake of the amino acid by the midgut.

Acute acidosis inhibits liver amino acid transport: no primary role for the urea cycle in acid-base balance

1994 ◽  
Vol 267 (6) ◽  
pp. F1015-F1020 ◽  
Author(s):  
L. Boon ◽  
P. J. Blommaart ◽  
A. J. Meijer ◽  
W. H. Lamers ◽  
A. C. Schoolwerth
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Hepatic Vein ◽  
Amino Acid Transport ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Primary Role ◽  
Urea Synthesis ◽  
Acid Transport ◽  
Acid Base

To examine further the role of the liver in acid-base homeostasis, we studied hepatic amino acid uptake and urea synthesis in rats in vivo during acute acidosis and alkalosis, induced by infusion of 1.8 mmol of HCl or NaHCO3 over 3 h. Amino acids and NH4+ were measured in portal vein, hepatic vein, and aortic plasma, and arteriovenous differences of amino acids and urinary urea and NH4+ excretion were measured. In acidosis, urinary urea excretion was reduced 36% (P < 0.01), whereas urinary NH4+ excretion increased ninefold (P < 0.01), but the sum of urea and NH4+ excretion was unchanged. Total hepatic amino acid uptake, as determined from arteriovenous differences, was decreased by 63% (P < 0.01) in acidosis, with the major effect being noted with alanine and glycine. Only glutamine was released in both acidosis and alkalosis but was not significantly different in the two conditions. Since intracellular concentrations of readily transportable amino acids were not different at low pH despite accelerated protein degradation, these results indicate that hepatic amino acid transport was inhibited markedly and sufficiently to explain the observed decrease in urea synthesis. Total hepatic vein amino acid content was greater in acidosis than alkalosis (P < 0.01). Directly or indirectly, by conversion to glutamine elsewhere, these increased amino acids were degraded in kidney and accounted for the ninefold increase in urinary NH4+ excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Use of [11C]Aminocyclohexanecarboxylate for the Measurement of Amino Acid Uptake and Distribution Volume in Human Brain

1990 ◽  
Vol 10 (5) ◽  
pp. 727-739 ◽  
Author(s):  
Robert A. Koeppe ◽  
Thomas Mangner ◽  
A. Lorris Betz ◽  
Barry L. Shulkin ◽  
Richard Allen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Human Brain ◽  
Amino Acid Transport ◽  
Normal Volunteer ◽  
Amino Acid Uptake ◽  
Distribution Volume ◽  
Transport Rate ◽  
Acid Uptake ◽  
Acid Transport ◽  
Influx Rate

A quantitative positron emission tomographic (PET) method to measure amino acid blood–brain barrier (BBB) transport rate and tissue distribution volume (DV) has been developed using 11C-labeled aminocyclohexanecarboxylate (ACHC), a nonmetabolized amino acid analogue. Dynamic PET data were acquired as a series of 15 scans covering a total of 60 min and analyzed by means of a two-compartment, two-parameter model. Functional images were calculated for the amino acid transport rate constants across the BBB and the amino acid DV in the brain. Results show [11C]ACHC to have an influx rate constant in gray matter of ∼0.03–0.04 ml g−1 min−1, indicating a single-pass extraction fraction of ∼5–7%. The intersubject coefficient of variation was ∼15% while intrasubject variability of repeat scans was only slightly greater than 5%. Studies were performed in 15 young normal volunteer control subjects, 5 elderly controls, 7 patients with probable Alzheimer's disease, and one patient with phenylketonuria. Results indicate that [11C]-ACHC will serve as the basis of a method for measuring amino acid transport rate and DV in the normal and pathological human brain.

Volume-regulatory amino acid transport in erythrocytes of the little skate, Raja erinacea

1993 ◽  
Vol 265 (1) ◽  
pp. R173-R179 ◽  
Author(s):  
J. K. Haynes ◽  
L. Goldstein
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Transport ◽  
Amino Acid Uptake ◽  
Disulfonic Acid ◽  
Acid Uptake ◽  
Gamma Aminobutyric Acid ◽  
Acid Transport ◽  
Beta Alanine ◽  
Volume Activation

Skate erythrocytes swell in a hypotonic medium and then reduce their volume mainly by releasing the beta-amino acids taurine and beta-alanine. Although these amino acids exhibit a net efflux, Na(+)-independent influx is also increased. Both the reduction in cell volume and increase in amino acid transport are inhibited by several inhibitors of band 3-mediated anion transport, including 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) [L. Goldstein and S. R. Brill, Am. J. Physiol. 260 (Regulatory Integrative Comp. Physiol. 29): R1014-R1020, 1991]. The objective of the present investigation was to further characterize the mechanism of volume-activated amino acid transport. Na(+)-independent amino acid uptake was studied because of the ease in controlling amino acid concentrations. Na(+)-independent taurine uptake was observed to be linear over a range of 0.1-15 mM and was not inhibited by 10 mM beta-alanine, suggesting that the transporter may be a channel rather than a carrier. The uptake of a variety of amino acids was examined to characterize the size of the putative channel. Glycine, beta-alanine, taurine, proline, gamma-aminobutyric acid (GABA), and threonine exhibited volume-activated transport that was DIDS inhibited, whereas aspartic acid, leucine, methionine, and ornithine were not transported. On the basis of the size of these amino acids, it appears that molecules containing eight or fewer major atoms and having a molecular mass of < 125-131 Da are transported during volume activation but larger molecules are not. We estimate the size of the channel to be 5.7-6.3 A in diameter.

Neutral amino acid transport systems of microvillous membrane of human placenta

1988 ◽  
Vol 254 (6) ◽  
pp. C773-C780 ◽  
Author(s):  
L. W. Johnson ◽  
C. H. Smith
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Transport ◽  
Plasma Membranes ◽  
Competitive Inhibition ◽  
Transport Systems ◽  
Acid Uptake ◽  
Acid Transport ◽  
Independent System ◽  
High Affinity

Placental transport produces concentrations of amino acids in fetal blood greater than those of maternal blood. Competitive inhibition studies of zwitterionic amino acid transport in isolated vesicles from the microvillous (maternal facing) plasma membranes of syncytiotrophoblast defined three transport systems: 1) a sodium-dependent system that supports methylaminoisobutyric acid (MeAIB) transport and has the characteristics of an A system; 2) a sodium-independent system with a high affinity for leucine and other amino acids with branched or aromatic side chains; and 3) a sodium-independent system with a preference for alanine as a substrate. The two sodium-independent systems could be further discriminated by marked specificity for trans stimulation with alanine or with leucine. System ASC, known to be present in whole placenta, and the neutral brush-border or imino systems of other polarized epithelia were apparently absent. Kinetic characteristics of the A system make it the probable primary driving force for concentrative transfer of its substrate amino acids to the fetus. Characteristics of the high-affinity leucine system demonstrated that it is saturated by normal serum leucine concentrations. Regulation of either system has the potential to alter placental amino acid uptake and transfer to the fetus.

Effect of low-protein diet-induced intrauterine growth retardation on rat placental amino acid transport

1996 ◽  
Vol 271 (1) ◽  
pp. C295-C303 ◽  
Author(s):  
M. S. Malandro ◽  
M. J. Beveridge ◽  
M. S. Kilberg ◽  
D. A. Novak
Keyword(s):  
Amino Acid ◽  
Amino Acid Transport ◽  
Basal Membrane ◽  
Amino Acid Uptake ◽  
Transport Processes ◽  
Acid Uptake ◽  
Acid Transport ◽  
Nutrient Delivery ◽  
Specific Amino Acid ◽  
Low Protein

Given the central role of the placenta in nutrient transport to the fetus, one might propose that maternal nutrition would have a regulatory effect on this nutrient delivery. We have examined the effect of a low-protein adequate-calorie diet on specific amino acid transport processes by the rat placenta. Maternal weight, fetal weight, and placental weight were all significantly reduced in dams fed a low-protein (5% casein), isocaloric diet when compared with dams pair-fed a control (20% casein) diet. Even though maternal serum amino acid levels were maintained in the low-protein animals, fetomaternal serum amino acid ratios were significantly reduced, suggesting a reduction in nutrient transfer to the fetus. Apical and basal membrane vesicles were isolated from the placental trophoblast and were used to examine the amino acid transport capacity of both maternal-facing and fetal-facing membranes, respectively. Na+-dependent neutral amino acid transport mediated by system A was decreased in both membrane preparations, while transport mediated by system ASC was unaffected. The Na+-dependent anionic amino acid uptake by system X(-)AG (EAAC1) was reduced on the basal membrane, while the Na+-independent component was similar between the low-protein and control diet-fed dams. Cationic amino acid uptake was also reduced on both membrane surfaces. A decreased steady-state mRNA content for EAAC1 and CAT1 (system y+) suggests that reduced synthesis of the transporter proteins is responsible for the decrease in transport activity. Taken together, these data support the hypothesis that maternal protein malnutrition affects nutrient delivery to the fetus by downregulation of specific amino acid transport proteins.

System A amino acid transport in incubated muscle: effects of insulin and acute uremia

1986 ◽  
Vol 251 (1) ◽  
pp. F74-F80
Author(s):  
B. J. Maroni ◽  
G. Karapanos ◽  
W. E. Mitch
Keyword(s):  
Amino Acid ◽  
Amino Acid Transport ◽  
Insulin Dose ◽  
Amino Acid Uptake ◽  
Similar Degree ◽  
Acid Uptake ◽  
Acid Transport ◽  
Insulin Resistant ◽  
System A ◽  
Stimulation Of

The insulin-stimulated increase in amino acid uptake in most cells and tissues involves stimulation of system A transport. In muscle the probes used to study this process have not been specific, making it difficult to determine whether system A is abnormal in insulin-resistant states, such as acute renal failure (ARF). To circumvent this problem, we studied 2-(methylamino) isobutyrate (MeAIB) transport. Its specificity for system A in incubated rat epitrochlearis muscles was documented by showing its uptake by only one carrier that is sodium dependent and insulin responsive and that exhibits adaptive regulation in response to starvation. Using this specific probe we determined whether insulin-stimulated amino acid transport by system A is impaired by ARF. MeAIB uptake was linear for 3 h in muscles of ARF and sham-operated (SO) rats. In the absence (basal) or presence of insulin, MeAIB uptake was significantly lower in ARF, yet the stimulation by insulin was similar in both groups. Likewise, the insulin dose-response relationship confirmed that physiological levels of insulin (less than or equal to 10(2) microU/ml) increased transport by a similar degree. At greater than or equal to 10(2) microU/ml insulin there was a plateau in MeAIB transport in ARF but not in SO muscles. Thus basal system A transport is depressed in ARF, but the stimulation of system A by physiological levels of insulin is preserved. At pharmacological levels of insulin system A transport is impaired by ARF.

Membrane transport of aromatic amino acids by Hymenolepis diminuta (Cestoda)

Parasitology ◽  
1980 ◽  
Vol 81 (2) ◽  
pp. 395-403 ◽  
Author(s):  
P. W. Pappas ◽  
H. R. Gamble
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Transport ◽  
Aromatic Amino Acid ◽  
Aromatic Amino Acids ◽  
Amino Acid Uptake ◽  
Hymenolepis Diminuta ◽  
Acid Uptake ◽  
Acid Transport ◽  
Concentration Difference

SUMMARYAromatic amino acids (phenylalanine, tryptophan and tyrosine) are absorbed by Hymenolepis diminuta through a combination of mediated (non-Na+-sensitive) transport and diffusion. All 3 amino acids are accumulated against an apparent concentration difference during a 30-min incubation of tapeworms in 0·1 mM 3H-labelled amino acid. Inhibitor studies demonstrate that phenylalanine, tryptophan and tyrosine are mutually competitive inhibitors of the uptake of each other, and the uptake of these amino acids is inhibited by aliphatic amino acids but not by basic or dicarboxylic amino acids. The D- and L-isomers of aromatic amino acids are equally effective in inhibiting aromatic amino acid uptake. The data indicate that at least 3 amino acid transport loci are involved in aromatic amino acid transport by H. diminuta.

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