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Biomedical subjects

H Schoemaker

Publications and source records attributed to H Schoemaker.

84 records · Page 5Linked to original sources
PubMed1982

High performance liquid chromatography of pharmacologically active amines and peptides in biological materials.

Precise and quantitative reversed-phase high performance liquid chromatographic (HPLC) procedures are described which can be used in biogenic amine and neuropeptide research. The amine procedure was applied to various pharmacological matrices including plasma, heart tissue and brain. The use of peptide HPLC as an analytical tool for various neuropeptides is illustrated by studies on des-tyrosine-gamma-endorphin (DT gamma E) metabolism in the brain and the stability of an ACTH (ORG-2766) analogue during a chronic infusion in rats. The power of HPLC as a research tool in peptide pharmacology is described, discussed and demonstrated as an aid in the understanding of the pharmacological effects of exogenous peptides and the function of the brain.

Adrenocorticotropic Hormone↗
PubMed1982

Synaptosomal uptake studies on recombinant inbred mice; neurotransmitter interaction and behavioral correlates.

The uptake of noradrenaline, choline and GABA into whole brain synaptosomes from the mice inbred strains C57BL/6By, BALB/cBy, their reciprocal crosses and seven recombinant inbred strains derived from the F2 crosses was measured in order to study the relation between different neurotransmitter systems and their possible correlations with behavioral parameters. Analysis of variance demonstrated significant differences in both Vmax and Km for each substrate between the inbred strains studied. Only the Km for GABA uptake did not reach significance although a strong trend (P = 0.07) was apparent. For none of the uptake parameters clear strain distribution patterns were found. A positive phenotypic as well as genotypic correlation was found between the Vmax and Km for noradrenaline, choline and GABA uptake. A genetic analysis showed a positive correlation between the Vmax for noradrenaline and choline uptake. Since prior to these neurochemical studies, all subjects were tested in a variety of behavioral paradigms, phenotypic and genotypic correlations between behavioral and neurochemical parameters could be calculated. The most consistent correlations were found between noradrenaline and choline uptake and water consumption and the preference ratio as measured in a conditioned taste aversion test.

Animals↗
PubMed1981

Differences in presynaptic alpha-blockade, noradrenaline uptake inhibition, and potential antidepressant activity between (+)- and (-)mianserin.

The effect of racemic mianserin on K+-evoked tritium release from rat brain cortex slices previously incubated with 3H-L-noradrenaline was studied. Racemic mianserin (10(-9)--10(-5) M) increased stimulation-induced release dose-dependently. As methysergide, metiamide, and cyproheptadine failed to do so, it was concluded that this effect was probably not caused by the antihistamine or antiserotonin activity of racemic mianserin, but due to its alpha-adrenolytic effect. Evaluation of the effects of the enantiomers (+)(S)mianserin and (-)(R)mianserin showed that the alpha-adrenolytic effect resided in the (+)isomer, whereas the (-)isomer was inactive at a concentration of 10(-6) M. Inhibition of noradrenaline into rat hypothalamic synaptosomes also showed stereospecificity in that (+)mianserin was about 300-times more active than(-)mianserin. Inhibition of rat muricidal behavior, a test for potential antidepressant activity, showed a similar dissociation in the effects of the two enantiomers, in that (+)mianserin was active, whereas (-)mianserin was not.

Adrenergic alpha-Antagonists↗
PubMed1981

Benzodiazepine receptor binding in young, mature and senescent rat brain and kidney.

Clinical reports have described age-altered pharmacological effects of anxiolytic drugs especially an increased susceptibility to their sedative actions. In order to test whether such changes may be due to age-related alterations in central benzodiazepine receptors, 3H-flunitrazepam binding was assayed in the frontal cortex and cerebellum of young, mature and senescent rats. The numbers of 3H-flunitrazepam binding sites and their affinity was determined by Scatchard analysis of saturation isotherms and the relative abundance of type I and type II benzodiazepine receptors was assessed by drug-inhibition studies using diazepam and the triazolopyridazine, CL 218,872. In addition, age related changes in the kidney and hippocampus of the Ro5-4864-sensitive benzodiazepine receptor were studied using 3H-Ro5-4864. No age-related alterations were noted in the binding characteristics of 3H-flunitrazepam. Furthermore, drug-inhibition of 3H-flunitrazepam binding by diazepam and CL 218,872 was nearly identical in young, mature and senescent rats, indicating that also the ratio of type I and type II receptors does not change with age. Binding of 3H-Ro5-4864 to membranes from rat hippocampus was not age-related. However, a significant decrease in 3H-Ro5-4864 binding to kidney membranes was demonstrated. Hence, central benzodiazepine receptors appear unaltered in the senescent rat model of aging. The clinical findings of an increased susceptibility to the sedative effects of benzodiazepines in the elderly may therefore be attributed to pharmacokinetic variables, or to events occurring secondarily to receptor activation.

Age Factors↗
PubMed1981

Immunodiagnosis of hepatitis B with high-affinity IgM monoclonal antibodies.

High-affinity monoclonal IgG and IgM antibodies to hepatitis B surface antigen (HBsAg) have been prepared and their functional capabilities explored by means of solid-phase radioimmunoassays. 125I-labeled HBsAg binding studies indicated that monoclonal IgM antibodies against HBsAg (anti-HBs) coupled to a solid-phase support quantitatively bound more HbsAg at a faster rate than conventionally prepared anti-HBs reagents or other high-affinity IgG monoclonal anti-HBs antibodies. Consequently, IgM anti-HBs was also radiolabeled, and an IgM-IgM radioimmunoassay was developed for the immunodiagnosis of hepatitis B. The lower limit of this assay was approximately 100 pg +/- 30 (SEM) of HBsAg per ml of serum. Compared to available commercial radioassays, preliminary studies have shown the IgM-IgM assay to have increased sensitivity, which improved the detection of a HBsAg-associated determinant in acute hepatitis and post transfusion hepatitis. It is probable that the multivalent interaction between monoclonal IgM anti-HBs and the polydeterminant HBsAg is important in augmenting the performance of this monoclonal assay.

Animals↗
PubMedDate not supplied

Characterization of in vitro proteolytic processing of beta-endorphin by reversed-phase HPLC.

In vitro, central and peripheral proteolytic processing of beta-endorphin by membrane-bound enzymes results in the formation of specific active fragments that have been recently shown to function in behavior, intestinal motility and in the central control of urinary bladder activity. A high resolution, reversed phase high performance liquid chromatography system capable of separating 28 beta-endorphin related fragments simultaneously was used to study the time-course processing of beta-endorphin by membrane associated peptidases in the brain and regions of the small intestine. The hypothesis we tested was that a homeostatic balance between alpha- and gamma-type endorphins exists in these tissues. The results of the study show that the rate and quantity of fragments produced between the mucosa and nerve-muscle regions of the small intestine are significantly different. Metabolic rates, pattern, and the ratio of alpha/gamma-type endorphins in the brain were very similar to the nerve-muscle region of the small intestine. This suggests that beta-endorphin processing to active fragments is occurring at the nerves of the small intestine and that a specific and similar balance of alpha/gamma-type endorphin exists in the brain and gastrointestinal system at neutral pH.

Animals↗
PubMedDate not supplied

Differential in vitro metabolism of beta-endorphin in schizophrenia.

Biologically active peptide fragments derived from the proteolytic cleavage of beta-endorphin (beta E) have been shown to be present in the brain. Based on clinical results using some of these fragments in neuropsychiatric disease studies we investigated the in vitro metabolism of beta E by twice-washed membrane homogenates of postmortem putamen from sex and age matched controls versus subjects with a diagnosis of schizophrenia. The present study demonstrates that frozen (-80 degrees C) postmortem human tissues are viable for these studies and that metabolism in control tissue proceeds similarly to fresh tissues. Furthermore, a significant increase in the formation of the putative neuroleptic-like peptide fragment des-enkephalin-gamma-endorphin in postmortem schizophrenic putamen versus controls was shown. A significant decrease in the formation of beta E was also reported. These data suggest that an approach using postmortem human brain is possible in studying beta-endorphin catabolism and is therefore applicable to other neuropeptide systems.

Adult↗