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Biomedical subjects

W Frick

Publications and source records attributed to W Frick.

At least 37 records · Page 2Linked to original sources
PubMed1984

Determination of neuropeptides in discrete regions of the rat brain by high-performance liquid chromatography with electrochemical detection.

High-performance liquid chromatography (HPLC) in combination with electrochemical detection (ED) is suitable for measuring accurately the levels of oxidizable neuropeptides in small samples of brain tissue. We have determined by HPLC-ED and a two-column-switching technique the levels of leucine- and methione-enkephalin in rat brain. By a sequential two-column HPLC-ED method we have also determined the levels of cholecystokinin tetrapeptide and octapeptide sulphate in various regions of the rat brain. The values found are in good agreement with those reported previously based on radioimmunoassay. We conclude that, due to its simplicity, HPLC-ED is an attractive alternative to existing methods for the determination of some neuropeptides in biological material.

Animals↗
PubMed1984

Acute administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) reduces dopamine and serotonin but accelerates norepinephrine metabolism in the rat brain. Effect of chronic pretreatment with MPTP.

Acute administration of MPTP (a synthetic heroin substitute) at 10-30 mg/kg (s.c.) produced 'Straub tail' phenomena, piloerection and reduced pelvis elevation in rats. The same dose decreased the concentrations of dopamine metabolites and reduced the rate of dopamine synthesis in the striatum. MPTP also reduced the metabolism of serotonin but accelerated that of norepinephrine in their corresponding terminal areas. The effects on central monoamines probably were not due to an agonistic action of MPTP on dopaminergic and serotonergic receptors, since MPTP only exhibited micromolar affinity to the corresponding binding sites. Furthermore, MPTP failed to induce rotational behavior in animals with unilateral nigrostriatal lesions. Chronic treatment of rats with MPTP (10 mg/kg s.c., daily for 3 weeks) did not result in massive degenerative changes in the nigrostriatal system. Histochemical analysis showed intact dopaminergic neurons. Striatal dopamine levels only were reduced by 10%. Dopaminergic neurons in rats chronically treated with MPTP responded normally to a pharmacological stimulus increasing their transmitter synthesis. Chronic treatment did not affect their response to an acute injection of MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1984

Classification of drugs according to receptor binding profiles.

The affinity for eight different neurotransmitter receptors of about forty drugs, used for the treatment of various central nervous system disorders, was determined following in vitro receptor binding assays. Our findings indicate that, in spite of widely varying chemical structures and often poorly understood mechanisms of action, the similarities in the "affinity profiles" permit a clinically meaningful classification of these drugs. Such an approach would thus be useful in the assessment of newly synthesized compounds at an early stage of drug development.

Animals↗
PubMed1984

Elucidation of the structure and receptor binding studies of the major primary, metabolite of dihydroergotamine in man.

The plasma concentrations and urinary excretion of dihydroergotamine and its metabolites have been measured after a single oral administration of 3 mg tritium-labelled drug to 6 male volunteers. The plasma level of non-volatile radioactivity declined biphasically with alpha- and beta-phase half-lives of 2.1 h and 32.3 h, respectively. The peak plasma concentration was reached within 3.2 h. Urinary excretion of total non-volatile radioactivity was low, amounting to 1.0% of the dose. The parent drug and four metabolites could be quantitated in urine and plasma samples. Metabolite 4 (8'-hydroxy-dihydroergotamine) was isolated from incubates of rat and monkey liver microsomal preparations. In human liver microsomal incubates, metabolite 4 was shown to be the primary metabolite of dihydroergotamine. In receptor binding studies performed with mammalian brain preparations, metabolite 4 had IC50-values at 6 monoaminergic binding sites similar to those of dihydroergotamine. Thus, it appears that the active principle consists at least of dihydroergotamine and its 8'-hydroxy derivative. As the concentration of metabolite 4 exceeded 5-7 times that of dihydroergotamine in urine and plasma, the bioavailability of dihydroergotamine should be reevaluated, taking into account the plasma concentrations of the parent drug and of its active metabolite, 8'-hydroxy-dihydroergotamine.

Animals↗
PubMed1983

Interaction of ergot alkaloids and their combination (co-dergocrine) with alpha-adrenoceptors in the CNS.

Co-dergocrine (Hydergine), composed of four dihydrogenated peptide ergot alkaloids (dihydroergocornine, dihydroergocristine, dihydro-alpha-ergokryptine and dihydro-beta-ergokryptine), has been reported to interact with alpha-adrenoceptors. The effect of the combination and its individual components on alpha-adrenoceptors subtypes in the rat brain was investigated in the present study. All five ergot drugs displaced [3H]rauwolscine, [3H]clonidine and [3H]WB 4101 from specific binding sites in membrane preparations from rat and bovine brain at nanomolar concentrations. In rat cerebral occipital cortex slices, the ergot drugs inhibited 1-noradrenaline-stimulated cyclic AMP formation (alpha 1-adrenoceptor test) and facilitated electrically evoked noradrenaline release (alpha 2-adrenoceptor test) at nanomolar concentrations. The results from the functional tests suggest that the ergot drugs have a slightly higher affinity to alpha 2-adrenoceptors which are antagonised in a competitive manner. The alpha 1-adrenoceptors are antagonised by the ergot drugs in a non-competitive manner. The relative order of potency at both receptor types was similar in that dihydroergocornine, dihydro-alpha-ergokryptine and dihydro-beta-ergokryptine were equipotent, whereas dihydroergocristine was less potent. The effect of the combination of the ergot alkaloids at both alpha-adrenoceptors appears to reflect the summation of the contributions of its components. The differences seen in the functional tests were less pronounced in the binding tests.

Animals↗
PubMed1983

Muscarinic receptors on intact, cultured neurons. Characterization by [3H]quinuclidinylbenzilate binding.

[3H]Quinuclidinylbenzilate (QNB) was used to identify muscarinic cholinergic receptors on intact, cultured neurons from fetal rat brains. Scatchard analysis revealed a single binding site with a dissociation constant Kd = approximately or equal to 170 pM. The rank order of potency of cholinergic drugs to displace [3H]QNB from intact neurons was similar to that observed using isolated membranes of brain homogenates. No difference in the rank order was observed with cultures of neurons from different brain regions which vary in their neuronal composition.

Animals↗
PubMed1983

Determination of cholecystokinin tetrapeptide and cholecystokinin octapeptide sulfate in different rat brain regions by high-pressure liquid chromatography with electrochemical detection.

A method for the determination of cholecystokinins in biological material, based on high-pressure liquid chromatography with direct electrochemical detection (HPLC-EC), is described. Using this method, the levels of cholecystokinin tetrapeptide and octapeptide sulfate in rat brain cortex, hippocampus, striatum, and brain stem were measured and found to be comparable to those reported using radioimmunoassay methods. We show that HPLC-EC is sensitive enough to accurately determine neuropeptides in brain tissue without prior derivatization and is therefore, due to its simplicity, an attractive alternative to existing methods.

Animals↗
PubMed1978

1-N-Acetylspermidine: occurrence in normal human serum.

Using gas chromatography mass spectrometry following derivatization (N-trifluoroacetylation), 1-N-acetylspermidine was found to occur in normal human serum at a level of approximately 0.008--0.5 nmol ml(-1), i.e. about two orders of magnitude lower than the corresponding spermidine level. No evidence for the occurrence in serum of the isomeric 8-N-acetylspermidine was found. Mass spectra of authentic samples of trifluoroactylated 1-N- and 8-N-acetylspermidine are presented.

Acetylation↗
PubMed1977

Sample derivatization and structure analysis by field desorption mass spectrometry. Peptide methylation-methanolysis.

Analysis by field desorption mass spectrometry of reaction product mixtures produced by treatment of peptides with methanol and hydrogen chloride augments significantly structural data derived by direct field desorption mass spectrometry analysis of the peptides. Analyses of data obtained by three peptides, beta-Ala-HisOH, p-Glu-Ser-GlyOH and Glu-Ser-Gly-AspOH are used for illustration. Data from field desorption mass spectrometry of peptide methylation-methanolysis product mixtures are used to (a) distinguish [M]+- from [M + H]+ in peptide field desorption mass spectrometry spectra, (b) ascertain the number of carboxyl groups present in a peptide, (c) identify a pyro-glutamyl N-terminus and (d) derive peptide sequence information. Definitive assignments of ion relationships are facilitated by use of methanol and deuteromethanol in paired experiments.

Mass Spectrometry↗