raf regulates the postnatal repression of the mouse alpha-fetoprotein gene at the posttranscriptional level.

The mouse alpha-fetoprotein (AFP) gene is transcribed at a high rate in liver during the second half of gestation. Its steady-state mRNA levels decrease 10(4)-fold shortly after birth, at least in part as the consequence of a dramatic decrease in its transcription rate. The final basal level of AFP mRNA in adult liver is influenced by a trans-acting locus on chromosome 15 termed raf.

The regulated expression of mRNA for Clara cell protein in the developing airways of the rat, as revealed by tissue in situ hybridization.

Tissue in situ hybridization has been used on sections of developing rat lung to follow the cellular sites of mRNA expression for a protein identified only in bronchiolar Clara cells. The mRNA for this Clara cell protein (CCP) was first detected on gestational day 16 in only one of the two types of tubules existing in the lung at this developmental stage. During the next 2 days CCP mRNA expression increased uniformly only in the epithelium lining the respiratory tubules.

Pregnancy in phenylketonuria: dietary treatment aimed at normalising maternal plasma phenylalanine concentration.

The transport characteristics of the placenta, which favour higher phenylalanine concentrations in the fetus than in the mother, and regression data of head circumference at birth against phenylalanine concentration at conception in maternal phenylketonuria (PKU), suggest that treatment of maternal PKU should ideally aim to maintain plasma phenylalanine concentration within the normal range throughout pregnancy. A patient with classical PKU was treated from before conception by aiming to maintain plasma phenylalanine concentration within the range 50-150 mumol/l and tyrosine within the range 60-90 mumol/l. The diet was supplemented with phenylalanine-free amino acids (100-180 g/day) and tyrosine (0-5 g/day).

Identification of a novel structural class of positive modulators of the N-methyl-D-aspartate receptor, with actions mediated through the glycine recognition site.

This study describes a new structural class of compounds which interact at the N-methyl-D-aspartate (NMDA) receptor-associated glycine recognition site. These E-gamma-substituted vinylglycine derivatives were active in displacing [3H]glycine binding from the NMDA receptor-associated recognition site in rat forebrain synaptic plasma membranes, with Ki values in the range of 0.24-8.

Cis-2,4-methanoglutamate is a potent and selective N-methyl-D-aspartate receptor agonist.

Cis- and trans-2,4-methanoglutamate were compared with L-glutamate as acidic amino acid ligands. Cis-2,4-methanoglutamate had a Ki of 0.052 microM against N-methyl-D-aspartate (NMDA)-specific L-[3H]glutamate binding compared with 0.

Differential modulation of the associated glycine recognition site by competitive N-methyl-D-aspartate receptor antagonists.

The competitive N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonopentanoate and two other five-atom linkage (C-5) omega-phosphono-alpha-amino acid analogs reduced [3H]glycine binding, in a dose-dependent manner, to a maximum of 45-55%, whereas seven-atom linkage (C-7) analogs had significantly less effect. The IC50 of the C-5 antagonists for the inhibition of [3H]glycine binding closely paralleled their potency both in displacing NMDA-selective L-[3H]glutamate binding and in negatively modulating (+)-[3H]5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne maleate ([3H]MK-801) binding. Additionally, reduction of glycine binding by the C-5 antagonists was reversed by both NMDA receptor agonists and C-7 competitive NMDA antagonists, providing evidence that the site of action of these C-5 antagonists is the NMDA recognition site, resulting in indirect modulation of the glycine site.

Characterization of D-3,4-cyclopropylglutamates as N-methyl-D-aspartate receptor agonists.

The 4 configurational isomers of D-3,4-cyclopropylglutamate (D-CGA) have been synthesized and analyzed for their interactions as excitatory amino acid recognition sites. Additionally, functional assessment of the action of these compounds at the N-methyl-D-aspartate (NMDA) receptor was performed. All 4 analogs function as agonists at the NMDA receptor as evidenced by their ability to stimulate [3H]MK-801 binding to the coupled PCP recognition site.

The ontogeny of alpha-fetoprotein gene expression in the mouse gastrointestinal tract.

The ontogeny of alpha-fetoprotein (AFP) gene expression has been examined in the fetal and adult mouse gastrointestinal tract. AFP mRNA constitutes approximately 0.1% of total mRNA in the fetal gut.

Neuropharmacological characterization of 1-aminocyclopropane-1-carboxylate and 1-aminocyclobutane-1-carboxylate, ligands of the N-methyl-D-aspartate-associated glycine receptor.

Following intravenous administration, 1-aminocyclobutane-1-carboxylate (ACBC, 100 mg/kg), a N-methyl-D-aspartate (NMDA)-associated glycine receptor antagonist, was eliminated with a T1/2 of 5 min in mouse brain and 4 min in rat cerebrospinal fluid (CSF). 1-Aminocyclopropane-1-carboxylate (ACC), a NMDA-associated glycine receptor agonist, was found to have a T1/2 of less than 5 min in mouse brain. ACC and ACBC did not alter basal cerebellar cGMP.

N-methyl-D-aspartate recognition site ligands modulate activity at the coupled glycine recognition site.

In synaptic plasma membranes from rat forebrain, the potencies of glycine recognition site agonists and antagonists for modulating [3H]1-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP) binding and for displacing strychnine-insensitive [3H]glycine binding are altered in the presence of N-methyl-D-aspartate (NMDA) recognition site ligands. The NMDA competitive antagonist, cis-4-phosphonomethyl-2-piperidine carboxylate (CGS 19755), reduces [3H]glycine binding, and the reduction can be fully reversed by the NMDA recognition site agonist, L-glutamate. Scatchard analysis of [3H]glycine binding shows that in the presence of CGS 19755 there is no change in Bmax (8.

Evidence for a functional coupling of the NMDA and glycine recognition sites in synaptic plasma membranes.

Activation of the N-methyl-D-aspartate (NMDA) receptor complex is subject to modulation via interactions at a coupled [3H]glycine recognition site in rat brain synaptic plasma membranes (SPM). We examined the effect of the potent and specific glycine site antagonists, 1-hydroxy-3-amino-2-pyrrolidone (HA-966) and 1-aminocyclobutane-1-carboxylate (ACBC), on the NMDA recognition site. These glycine analogs were found to significantly stimulate the binding of the competitive NMDA antagonist, [3H]3-(2-carboxypiperazin-4-y1)propyl-1-phosphonate ([3H]CPP) in a dose-dependent fashion, whereas both compounds inhibited NMDA-specific L-[3H]glutamate (agonist) binding.

Guanine nucleotide modulation of [3H]TCP binding to the NMDA receptor complex.

Guanine nucleotides have been examined for their effect on [3H]1-[1-(2-thienyl)-cyclohexyl]-piperidine ([3H]TCP) binding to rat forebrain synaptic plasma membranes (SPM). We report that of the series of guanine nucleotides tested, GTP, GDP, 5'-guanylylimidodiphosphate (Gpp(NH)p) and 5'-guanylylmethylenediphosphate (Gpp(CH2)p) are significantly more potent at decreasing [3H]TCP binding than GMP, cyclic GMP, and guanosine. GTP, the most potent compound tested, inhibited basal [3H]TCP binding with an IC50 of 38.

Characterization of a [3H]glycine recognition site as a modulatory site of the N-methyl-D-aspartate receptor complex.

A [3H]glycine recognition site in rat brain synaptic plasma membranes (SPM) has been identified, having characteristics expected of a modulatory component of the N-methyl-D-aspartate receptor complex. Incubation of SPM with [3H]glycine for 10 min at 2 degrees C results in saturable, reversible binding with a KD of 0.234 microM and a Bmax of 9.