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Biomedical subjects

A C Neethling

Publications and source records attributed to A C Neethling.

At least 19 recordsLinked to original sources
PubMed1984

Possible modulation of phosphorylation of acetylcholine receptor-enriched membrane preparations.

During phosphorylation of acetylcholine receptor (AChR)-enriched membrane preparations from Torpedo fuscomaculata , phosphate is incorporated into a single protein, with a molecular weight corresponding to that of one of the receptor subunits (37,000 daltons). This protein also seems to contain the receptor binding site. ATP binds to four protein species, one of which corresponds to a different subunit of the receptor (molecular weight 45,000). Phosphorylation of these membrane preparations is affected by several factors, known to be involved in postsynaptic events. Ca2+ (10 microM) inhibits the reaction, whereas cGMP (20 microM), causes stimulation. Furthermore it has been shown that the agonists, acetylcholine, and carbamylcholine (10 microM and 1 microM) stimulate the phosphorylation reaction, while the antagonists, tubocurarine, hexamethonium, and decamethonium (1 microM), cause inhibition.

Acetylcholine↗
PubMed1983

Phosphorylation increases alpha-bungarotoxin binding to acetylcholine receptor-enriched membrane preparations.

Acetylcholine receptor (AChR)-enriched membrane preparations from Torpedo electroplax bind alpha-bungarotoxin with a KD of 8.4 nM and the concentration of binding sites is 16 pmoles/mg protein. When, however, the alpha-toxin is incubated with receptor samples, phosphorylated in the presence of Mn2+ (10 mM) and ATP (0.5 mM), the concentration of binding sites is increased to 94 pmoles/mg protein, although there is no marked change in the KD (11 nM). Binding of acetylcholine to AChR-enriched membrane preparations occurs at a receptor which has two different conformational states with KD's of 8.4 nM and 520 nM. The concentration of binding sites for the high affinity component is 1.35 pmoles/mg protein and for the low affinity component is 12 pmoles/mg protein. The effect of phosphorylation of the AChR on agonist binding could not be determined.

Acetylcholinesterase↗
PubMed1983

Ontogeny and sexual dimorphism of estradiol-2-hydroxylase activity in rat liver microsomes.

A radio-enzymatic method was used to measure the activity of estradiol-2-hydroxylase in liver microsomes of male and female Wistar rats, ranging in age from 10 to 63 days. In pre-pubertal rats (10-30 days) the Vmax increased, but revealed no sex differences. After 30 days of age, however, it decreased in females. In males, on the other hand, it increased still further, reaching a maximum in adulthood. The apparent Km showed no significant sex differences in pre-pubertal rats, but appeared to decline after puberty in females. In females puberty was also associated with the appearance of important changes in the kinetic properties of estradiol-2-hydroxylase. These changes were reflected in hyperbolic Lineweaver-Burk plots. Hill plots of this data gave straight lines with slopes significantly less than one--indicating negative cooperativity. Alternatively the hyperbolic Lineweaver-Burk plots could mean that the enzyme consists of more than one form, which act on the same substrate, but with different affinities. It is concluded that development in female Wistar rats is associated with important qualitative changes in the kinetic properties of estradiol-2-hydroxylase and that factors which become operative during puberty play a key role in initiating these changes.

Aging↗
PubMed1983

A possible role for phosphorylation of the acetylcholine receptor.

The acetylcholine receptor (AChR) from Torpedo fuscomaculata can be phosphorylated. This reaction was fully characterised. In addition, the influence of factors with possible modulatory effects on the phosphorylation of this receptor were investigated. In order to suggest the possible role of phosphorylation in neurotransmission, the effects of this reaction on the binding of ligands to the AChR were investigated. It was found that phosphorylation enhanced the binding of the antagonist, alpha-bungarotoxin to the AChR. Due to experimental difficulties the effect on binding of the agonist, acetylcholine, to the receptor, could not be determined. However, a hypothesis is proposed regarding the role of phosphorylation of the AChR in neurotransmission.

Acetylcholine↗
PubMed1982

Characterization of protein phosphorylation in acetylcholine receptor-enriched membrane preparations from Torpedo fuscomaculata.

When the acetylcholine receptor (AChR) from Torpedo is phosphorylated, ATP is found to bind non-covalently to the preparation. After correction is made for this binding of ATP, the phosphorylation reaction has a Km of 0,16 mM, a pH optimum of 8,6 and reaches maximal activity within 3 min. The intrinsic kinase activity is very specific for the AChR and does not phosphorylate either histones or phosvitin. The only amino acid to be phosphorylated is serine and cyclic GMP causes stimulation of the reaction.

Acetylcholine↗
PubMed1982

Cyclic AMP independent protein kinase activity in rat cerebral cortex synaptic vesicles--partial characterization.

The intrinsic protein kinase activity of a highly purified synaptic vesicle preparation was characterized. The time-course of the reaction was found to be rapid and linear for about 1 min, but plateaued after 30 min by which time approximately 1 nmol of 32P per mg protein was incorporated into trichloroacetic acid precipitated vesicular protein. The enzyme was optimally active at pH 6.0 (37 degrees C), and had apparent Km values of 40 and 88 microM for ATP and GTP respectively. The enzyme was not stimulated by cAMP or cGMP. Mg2+ was required for maximal activity. The reaction was inhibited by free Ca2+, and non-selectively by Na+, K+, and NH4+.

Animals↗
PubMed1981

Sex-dependent differences in phenobarbitone-induced oestradiol-2-hydroxylase activity in rat liver.

Oestradiol-2-hydroxylase (E2-OH) activity was measured in live and brain microsomes of 6-8-week-old Wistar rats. Phenobarbitone (75 mg/kg daily for 3 days) significantly increased enzyme activity in the liver of males and females, but there were striking differences between the two sexes. In males the enzyme activity was increased by 37% over control values and in females by 200%. The total microsomal cytochrome P-450 content was increased by 75% in males and by 82% in females. the apparent Michaelis constant (Km) of E2-OH for 17 beta-oestradiol in untreated males (9.8 microM) and females (9.2 microM) did not differ significantly. Phenobarbitone treatment, however, tended to reduce the apparent Km in males (8.2 microM) and to increase it in females (18.7 microM). E2-OH activity was also detected in brain tissue of both sexes, but it was 50-200-fold lower than in the liver and was not increased by phenobarbitone.

Animals↗
PubMed1981

[Mechanism of delta-aminolevulinic acid neurotoxicity].

The neurotoxicity of delta-aminolaevulinic acid (ALA), porphobilinogen (PBG), glutamic acid, gamma-aminobutyric acid and kainic acid was compared in order to investigate the possibility of a common neurotoxic mechanism. Only ALA (10 microM) and glutamic acid (1 mM) were toxic towards neurons in culture, as measured by cell survival after 5 days' exposure. 3H-kainic acid binds to striatal membranes with an equilibrium dissociation constant (KD) of 57 nM and the number of binding sites was found to be 20 pmol/g striatal tissue. However, neither of the porphyrin precursors could displace kainic acid from these binding sites. Kainic acid alone caused neuronal degeneration after intrastriatal administration, as determined by 3H-spiroperidol binding to striatal membranes. The porphyrin precursors ALA and PBG thus do not share a common neurotoxic mechanism with the well-known neurotoxin kainic acid.

Aminolevulinic Acid↗
PubMed1981

Effects of four prostaglandin analogues on menstrual cycle length and peripheral levels of 17 beta-oestradiol and progesterone in the chacma baboon.

Four different prostaglandin analogues were studied with regard to their effects on menstrual cycle length and peripheral in th chacma baboon (Papio ursinus). Pooled data showed that the luteal phase was shortened by more than 4 days and that both hormone levels were reduced significantly after treatment. In terms of the inhibition of progesterone production as an absolute index of corpus luteum function, PGF2 alpha, 1,15-lactone, and 11 alpha (15S)-17-phenyl-ent-18-19,20-trinor-PGE2 methyl ester were found to be the most effective luteolytic compounds.

Animals↗
PubMed1981

gamma-Aminobutyric acid concentration in cerebrospinal fluid in schizophrenia.

gamma-Aminobutyric acid (GABA) concentration was determined in cerebrospinal fluid (CSF) of acute and chronic schizophrenic patients, in persons with psycho-organic or personality disorders, and in nonpsychiatric controls. The mean CSF GABA level in the chronic schizophrenic patients was found to be significantly higher than in any of the other groups. No other statistically significant differences were found. Statistical analysis revealed that the elevated CSF GABA concentration in the chronic schizophrenic patients was unlikely to be caused by medication. These results are interpreted as evidence for possible primary or secondary GABAergic overactivity in the brain in chronic schizophrenia.

Acute Disease↗
PubMed1980

[Catechol estrogens].

Hydroxylation of oestrogens in the 2 or 4 positions leads to the formation of catechol oestrogens. These compounds are physiologically active in animals, especially in the control of gonadotropin secretion. Physiological activity can be ascribed to either an oestrogenic action or interaction with the catecholaminergic systems. These compounds are also formed in human subjects. Surprisingly high levels are found in the urine. The peri-ovulatory peak in urinary catechol oestrogen excretion is compatible with a role for these compounds in the control of gonadotropin secretion.

Animals↗
PubMed1977

Isovaleric acidaemia in two South African children.

Two siblings who were repeatedly admitted to hospital with acute episodes of vomiting, dehydration and coma were found to be suffering from isovaleric acidaemia. This condition is a rare inherited abnormality of leucine metabolism, which is frequently fatal in the early weeks of life and leads to mental retardation in a high proportion of those who survive early attacts. However, both our patients were of normal intelligence. The clinical presentation, biochemical defect, diagnosis and suggested therapies are reviewed.

Acute Disease↗
PubMed1977

Pathogenesis of neural manifestations in acute porphyria.

At least 4 possible mechanisms may be postulated to explain the neural manifestations of acute porphyria in the hereditary hepatic porphyrias. These are (i) excessive amounts of porphyrins or porphyrin precursors produced in the liver during acute attacks are transported to the central and peripheral nervous system, where they exert neurotoxic effects; (ii) unidentified metabolites of the aforementioned compounds may be responsible; (iii) in patients with these diseases there may be a metabolic defect in neural haem biosynthesis which is aggravated by precipitating factors, thereby leading to acute neural manifestations; and (iv) the hepatic and nervous system lesions may be metabolically quite unrelated. Each of these possibilities is considered, and evidence is adduced that a genetic defect in haem biosynthesis in the nervous system is the most plausible hypothesis.

5-Aminolevulinate Synthetase↗
PubMed1977

Effects of hexachlorobenzene feeding and iron overload on enzymes of haem biosynthesis and cytochrome P 450 in rat liver.

1. The effect of hexachlorobenzene feeding on liver delta-aminolaevulinate synthase, uroporphyrinogen decarboxylase and cytochrome P 450 was studied at various time-intervals in siderotic and non-siderotic rats. 2 In the non-siderotic group hexachlorobenzene feeding led to a progress decrease in liver uroporphyrinogen decarboxylase activity, accompanied by a progressive increase in delta-aminolaevulinate synthase activity. Cytochrome P 450 concentrations were above normal throughout but fell toward the end of the experiment. 3. Similar but more marked changes were found in the siderotic animals. The fall in uroporphyrinogen decarboxylase activity occurred earlier and was significantly greater in these animals, whereas the increase in delta-aminolaevulinate synthase activity was consistently larger. Liver cytochrome P 450 concentration also rose but to a lesser extent than that in the non-siderotic rats. 4. Hexachlobenzene-induced porphyria would seem to be attributable to inhibition or inactivation of hepatic uroporphyrinogen decarboxylase. Hepatic siderosis has a synergistic effect with hexachlorobenzene on this enzyme and may exert additional effects by promoting cytochrome P 450 turnover.

5-Aminolevulinate Synthetase↗