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Biomedical subjects

U Wollert

Publications and source records attributed to U Wollert.

At least 37 records · Page 2Linked to original sources
PubMed1980

Inhibition of GABA and benzodiazepine receptor binding by penicillins.

Penicillins are thought to be GABA receptor antagonists. In order to determine the affinities of various penicillin derivatives for the GABA receptor, their potencies as inhibitors of specific [3H]GABA binding to rat brain membranes were investigated. All investigated penicillins inhibit specific [3H]GABA binding, with IC50 values ranging from 2 to 60 mM. The results are consistent with the assumption that penicillins are weak GABA receptor antagonists.

Animals↗
PubMed1979

A highly reactive tyrosine residue as part of the indole and benzodiazepine binding site of human serum albumin.

The interaction of L-tryptophan and four benzodiazepine derivatives with tyrosine-modified human serum albumin was investigated by equilibrium dialysis and circular dichroism measurements. Out of the 18 tyrosine residues of the human serum albumin molecule, only 9 could be modified with tetranitromethane. At least up to a degree of modification of 5, the conformation of human serum albumin was not changed and no crosslinking and fractionation has been found, as revealed from circular dichroism measurements in the far ultraviolet range and from SDS polyacrylamide electrophoresis. The modification of only 2 out of the 9 accessible tyrosine residues of human serum albumin strongly affects the binding of L-tryptophan and diazepam to their common, stereospecific bindining site. This was evidently shown by a reduction of the association constants by more than 90% and by a large reduction of the extrinsic Cotton effects of four benzodiazepines bound to human serum albumin. The numbers of binding sites remained unchanged. Strong evidence was presented that only one tyrosine residue, which reacts faster with tetranitromethane than all others, is mainly involved in the specific indole and benzodiazepine binding site of human serum albumin. The location of this highly reactive tyrosine residue and that of the specific indole and benzodiazepine binding site within the human serum albumin primary structure is discussed.

Benzodiazepines↗
PubMed1979

Human serum albumin as a 'silent receptor' for drugs and endogenous substances.

Most drugs are bound to human serum albumin (HSA) via a few high affinity binding sites and several sites of much lower affinity. There is now increasing evidence that the actual number of high affinity drug-binding sites of HSA is rather small. Thus, each of these binding sites binds several drugs of very different chemical and pharmacological properties with relative high affinity. On the other hand these drug-binding sites can in some cases be very specific and even stereoselective, as demonstrated by the stereospecific binding of drugs to some of these binding sites. The discrepancy between both observations can be explained by the conformational adaptability of the HSA-binding sites.

Benzodiazepines↗
PubMed1978

Benzodiazepine receptor binding: the interactions of some non-benzodiazepine drugs with specific [3H] diazepam binding to rat brain synaptosomal membranes.

The interaction of several non-benzodiazepine drugs with [3H] diazepam binding to benzodiazepine receptors in rat brain synaptosomal membranes was investigated. Baclofen, benzoctamine, hydroxyzine, chlorpromazine, haloperidol, imipramine, and amitriptyline displace specific [3H] diazepam binding, but the concentrations needed are too high to explain pharmacological effects of these drugs by an interaction with benzodiazepine receptors. The most potent non-benzodiazepine drug for inhibiting specific [3H] diazepam binding was methaqualone (IC50 value of 150 micrometer). It is suggested that interactions with benzodiazepine receptors may account for the anxiolytic and anticonvulsive side effects of this drug. The analeptic drug pentylenetetrazole interacts with benzodiazepine receptor binding with an IC50 value of about 1 mM, which is possibly too high to explain its convulsive properties by an antagonism at the benzodiazepine receptor.

Animals↗
PubMed1978

The modification of the lone tryptophan residue in human serum albumin by 2-hydroxy-5-nitrobenzyl bromide. Characterization of the modified protein and the binding of L-tryptophan and benzodiazepines to the tryptophan-modified albumin.

The possible function of the lone tryptophan residue of human serum albumin in the stereospecific binding site for indole and benzodiazepine compounds was investigated by chemical modification. This residue can be selectively modified with 2-hydroxy-5-nitrobenzyl bromide. The modification alters the conformation of the albumin only slightly, as revealed by circular dichroism, fluorescence, and ultraviolet absorption measurements. A decrease in the association constants of L-tryptophan and diazepam of about 30 - 50% and a decrease in the extrinsic Cotton effects of four benzodiazepine derivatives of about 10 - 15% were found as specific effects of the tryptophan modification. The tryptophan modification itself did not change the number of binding sites of diazepam and L-tryptophan. It is suggested that the lone tryptophan residue of human serum albumin is not directly involved in the specific binding site for indole and benzodiazepine compounds. However, the modification alters the properties of the binding site either by an incomplete refolding of the albumin after urea treatment, or a more selective allosteric effect of the modified tryptophan residue.

2-Hydroxy-5-nitrobenzyl Bromide↗
PubMed1978

The influence of increasing albumin concentrations on the determination of the binding of sulfamethoxy-pyridazine to human and bovine serum albumin.

The binding of sulfamethoxypyridazine to human and bovine serum albumin was determined at eight constant molar drug/albumin ratios for seven different albumin concentrations ranging from 0.1% to 1.5%. The serum albumin concentration affects the determination of the albumin binding of the drug in two different ways. 1. The relative affinity of the albumins for the drug increases with increasing albumin concentrations, while the numbers of binding sites remain constant. 2. The association constants taken from Scatchard plots decrease with increasing albumin concentrations. It is concluded that a direct comparison of binding constants obtained with different albumin concentrations, as widely done, can lead to misinterpretations and should be avoided.

Animals↗
PubMed1976

Spectroscopic studies on the complex formation of suramin with bovine and human serum albumin.

The binding of suramin to bovine and human serum albumin was investigated by gel filtration and spectroscopic measurements. Besides some low-affinity binding sites suramin has, on the bovine serum albumin molecule one and on the human serum albumin molecule two, high-affinity binding sites. Spectroscopic measurements reveal that there are large differences between the albumins in the mechanism of binding to the high-affinity binding sites. Further, it is suggested that high concentrations of suramin provoke an unfolding of the albumin moleculse. In order to explain the unusual behaviour of suramin in connection with the displacement of other ligands from the albumin binding the fluorescence probe 1-anilino-8-naphthalenesulfonic acid (ANS) was employed as a reporter group molecule for fluorescence as well as circular dichroism measurements. By these measurements it could be shown that suramin greatly influences the microorganization of both albumin molecules. In the case of these measurements large differences between bovine and human serum albumin were also found.

Anilino Naphthalenesulfonates↗
PubMed1976

Circular dichroism studies on the interaction of sulfonylureas with insulin.

The interaction of 5 sulfonylurea derivatives with insuline was investigated by means of circular dichroism measurements. It was found that all sulfonylureas investigated decrease the ellipticity band of insulin at 208 nm, whereas the band at 222 nm remains unaffected. It is suggested that these observations are due to a change of the insulin conformation, provoked by the interaction of the drugs with insulin. It is assumed that such an effect on the insulin conformation can influence the binding properties of insulin, e.g. in respect to the insulin aggregation, to the binding to insulin antibodies and to a bound, inactive form of insulin in the plasma. Some other drugs have similar, but mostly smaller effects on the CD spectrum of insulin. Therefore, the importance of these observations for the hypoglycaemic action of the sulfonylureas is not yet clear.

Animals↗
PubMed1975

Benzodiazepines: specific competitors for the binding of L-tryptophan to human serum albumin.

By means of the gel filtration technique, the effect of nine benzodiazepine derivatives on the binding of L-tryptophan to human serum albumin was investigated. Using equimolar tryptophan and benzodiazepine concentrations, all benzodiazepines with binding constants higher than 10(4) (M(-1), displace L-tryptophan from its binding site to a high degree. The mechanism of the displacement was characterized as a competition for a common binding site. Some of the benzodiazepines displace L-tryptophan to a greater extent than salicylic acid. The benzostereospecific binding to human serum albumin. This study shows that there is only one binding site on the human serum albumin molecule, which binds tryptophan and the benzodiazepines in a highly stereospecific manner. Therefore it is concluded that the benzodiazepines and L-tryptophan must have similarities in their molecular structure, so that both can bind to the common binding site in such specific manner. These considerations are discussed in regard to the known influence of benzodiazepine derivatives on the L-tryptophan metabolism in brain. A direct involvement of the reported displacement in the pharmacological actions of the drugs seems not to be relevant because of their small therapeutical plasma levels.

Animals↗