Failure of 2 Hydroxyestradiol to interact with dopamine inhibition of human prolactin secretion in vitro and with dopamine receptors of prolactin-secreting adenomas

The ability of 2-Hydroxyestradiol, a catecholestrogen, and 17 beta Estradiol to interact with the dopamine inhibition of prolactin and with dopamine receptors has been tested on dispersed human prolactin-secreting cells obtained from ten pituitary adenomas. There is a 80% inhibition of prolactin secretion obtained by addition of dopamine in a superfusion system. This inhibition is not affected by preexposure to the steroids, or by their introduction into the perifusion medium. Moreover 2 Hydroxyestradiol and 17 beta Estradiol do not interact with the binding of 3H Domperidone to DA receptors.     

Translational inhibition by heme of the synthesis of hepatic δ-aminolevulinate synthase in a cell-free system

Synthesis of δ-aminolevulinate synthase in a rabbit reticulocyte lysate system directed by total polysomes from the liver of allylisopropylacetamide-treated rats was studied with the combined use of [³H]leucine and a specific rabbit antibody. The protein synthesis observed in the cell-free system employed represented mainly the peptide chain elongation and its termination rather than the net synthesis involving initiation. Synthesis of δ-aminolevulinate synthase in this cell-free system was inhibited progressively with the increased addition of hemin; the synthesis was reduced to about 40% by about 30 μM hemin. Synthesis of total protein, however, was not significantly affected by the addition of hemin. The data obtained suggest that heme inhibits a peptide chain elongation step in the synthesis of δ-aminolevulinate synthase.     

Interaction of the inhibitor of the 3',5' cyclic AMP phosphodiesterase of Dictyostelium discoideum with the Affi-Gel blue

Disodium ethylenediamine tetraacetic acid and/or allylisopropylacetamide administration to rat pups did not evoke a premature induction of hepatic δ-aminolevulinic acid synthetase. Administration of iron to adult rats did not alter δ-aminolevulinic acid synthetase activity and had little inductive effect on heme oxygenase activity. Both heme and cobalt/dextran rapidly induced microsomal heme oxygenase by 3–8 fold. Induction of heme oxygenase by heme could be totally blocked by concurrent administration of cycloheximide. These results argue against the hypothesis that iron is the physiological mediator of δ-aminolevulinic acid synthetase activity.     

cAMP-dependent induction of delta-aminolevulinate synthase in isolated embryonic chick liver cells.

Isolated liver cells were prepared from 17-day old chick embryos and incubated in Eagle's basal medium. Induction of δ-aminolevulinate synthase activity occurred immediately upon addition of allylisopropylacetamide and was totally dependent on the presence of Bt₂cAMP (or cAMP) during the first 6 h of incubation. Under optimal inducing conditions in the presence of desferrioxamine mesylate and hormones, δ-aminolevulinate synthase induction occurred at rates comparable with those observed in ovo. The isolated liver cells provide a convenient experimental system for studying the effect of porphyrogenic drugs on porphyrin metabolism.     

Effects of volatile anaesthetics on heme metabolism in a murine genetic model of Acute Intermittent Porphyria. A comparative study with other porphyrinogenic drugs

Background

Acute Intermittent Porphyria (AIP) is an inherited disease produced by a deficiency of Porphobilinogen deaminase (PBG-D). The aim of this work was to evaluate the effects of Isoflurane and Sevoflurane on heme metabolism in a mouse genetic model of AIP to further support our previous proposal for avoiding their use in porphyric patients. A comparative study was performed administering the porphyrinogenic drugs allylisopropylacetamide (AIA), barbital and ethanol, and also between sex and mutation using AIP (PBG-D activity 70% reduced) and T1 (PBG-D activity 50% diminished) mice.

Cytochrome P-450 and halothane metabolism. Decrease in rat liver microsomal P-450 in vitro

Anaerobic in vitro incubation of microsomes from phenobarbital(PB)-induced rats with halothane results in an irreversible decrease of measurable cytochrome P-450. There is a parallel decrease in heme content under the same incubation conditions. However, microsomes from 3-methylcholanthrene(3-MC)-induced or untreated animals do not show a reduction in cytochrome P-450 content. Aerobic incubation with halothane results in a decrease of cytochrome P-450 which can be completely reversed by dialysis or the addition of potassium ferricyanide. These latter treatments only partially restore the cytochrome P-450 levels following anaerobic incubations. The decrease in cytochrome caused by halothane is not associated with measureable heme N-alkyl adduct formation; lipid peroxidation does not play a role as indicated by the lack of effect of 1 mM EDTA or a decrease in glucose-6-phosphatase activity. Halothane metabolites are bound irreversibly to microsomal protein as determined by gel electrophoresis only when the oxygen concentration is very low. The mechanism of cytochrome P-450 decrease is consistent with the formation of a reactive metabolite which binds to the protein portion and also destroys heme.     

The effect of beta-adrenergic blocking agents on experimental porphyria induced by 3,5-diethoxycarbonyl-1,4-dihydrocollindine (DDC) in vivo and in vitro

The effect of DL-propranolol on 3′,5′-diethoxycarbonyl-1,4-dihydrocollidine-induced experimental porphyria was studied.dl-Propranolol, a beta-adrenergic blocking agent with non-specific membrane effects, partially inhibited 3′,5′-diethoxycarbonyl-1,4-dihydrocollidine-induced delta-aminolevulinate synthetase activity both in rats and in chick embryo liver cells in culture.In rats, DL-propranolol decreased urinary delta-aminolevulinate and porphobilinogen but no change occurred in the 24-h urinary excretion of total porphyrins and in the concentration of porphyrins in the liver. In cultured chick embryo liver cells treated with 3′,5′-diethoxycarbonyl-1,4-dihydrocollidine, DL-propranolol decreased accumulation of porphyrins in the medium.d-Propranolol, oxprenolol and quinidine acted like dl-propranolol in chick embryo liver cells in culture treated with 3′,5′-diethoxycarbonyl-1,4-dihydrocollidine. Pindolol, practolol and lidocaine had no effect.Phenobarbitone had a synergistic effect on the induction of delta-aminolevulinate synthetase by 3′,5′-diethoxycarbonyl-1,4-dihydrocollidine in cultures of chick embryo liver cells. This induction was partially inhibited by propranolol. However, the increased accumulation of porphyrins in the medium caused by 3′,5′-diethoxycarbonyl-1,4-dihydrocollidine was inhibited by the addition of phenobarbitone. This inhibited induction was further decreased by propranolol.Most of our results indicate that the drugs tested act mainly by their effects on membranes.     

delta-Aminolevulinate synthase isozymes in the liver and erythroid cells of chicken

Antibodies raised against the purified chicken liver delta-aminolevulinate synthase showed a partial cross-reactivity with the chicken erythroid delta-aminolevulinate synthase. delta-Aminolevulinate synthase synthesized in vitro using polysomes from erythroid cells showed a subunit molecular weight of 55,000, whereas the enzyme synthesized in vitro using liver polysomes had a subunit molecular weight of 73,000. delta-Aminolevulinate synthase isolated from mitochondria of erythroid cells showed a molecular weight of 53,000, while the enzyme in liver mitochondria had a value of 65,000. These observations imply that the erythroid delta-aminolevulinate synthase differs from the hepatic enzyme.