Search PubMed⌕ Search

Biomedical subjects

R Morgenstern

Publications and source records attributed to R Morgenstern.

At least 163 records · Page 9Linked to original sources
PubMed1983

LSD-potentiated apomorphine hypermotility: a model for differentiating antipsychotic drugs.

The model of LSD-potentiated apomorphine hypermotility (LPAH) in rats in comparison to apomorphine-induced hypermotility (AH) was used to investigate typical and atypical neuroleptics by analyzing complete dose response curves. Haloperidol (0.06 mg/kg) induced a parallel shift to the right of both the AH and LPAH dose response curves indicating dopaminolytic properties without any serotonolytic effect. Chlorpromazine (0.5 mg/kg) caused a mixed inhibitory effect on the LPAH, whereas the AH was not affected, probably due to the variety of actions at different transmission systems. Clozapine (0.125 mg/kg) antagonized the LSD effect indicating serotonolytic properties, whereas an additive influence on the AH might be caused by its cholinolytic properties. Sulpiride (10 mg/kg) potentiated both the AH and the LPAH, probably due to presynaptic dopaminergic mechanisms. Two conclusions can be drawn: (1) The results agree with and support the idea of a serotonergic modulation of the (predominant) mesolimbic dopaminergic system in the induction of locomotor effects. (2) The model of LPAH is useful to clearly differentiate typical from atypical neuroleptics, and to obtain information whether there is a primary involvement of dopaminergic or serotonergic mechanisms.

Animals↗
PubMed1983

[Locomotor activity and the nucleus accumbens].

Locomotor hyperactivity in rats was induced by microapplication of apomorphine (1 microgram/microliter) or picrotoxin (0.5 microgram/microliter) bilaterally into the n. accumbens and measured in an open field test. After systemic administration, the dopaminolytic drug haloperidol in doses between 0.06 and 0.25 mg/kg abolished both types of hypermotility. After an intraaccumbens injection of haloperidol (0.4 microgram/microliter, bilaterally) or carbachol (1.0 microgram/microliter, bilaterally), the apomorphine hypermotility was completely suppressed whereas the picrotoxin effect remained unchanged. Scopolamine which is known to induce hypermotility after systemic administration was, as methylatropine (1.0 mu/microliter bilaterally), too, without any locomotor effect after intraaccumbens injection. The locomotor inhibitory effect of haloperidol is discussed to be not restricted to its dopaminolytic action within the n. accumbens.

Animals↗
PubMed1983

[Degenerative changes in the occipital neocortex in chronically amphetamine treated rats].

Neurons of the Wistar-rats' occipital cortex were morphologically investigated after chronical application of amphetamine. The nerve cells impregnated according to the Golgi-Kopsch technique showed in part changes on both the dendrites and in the axonal region. Besides a partial reduction of spines and of peripheral dendritic arborizations round varicosities of different density could be observed on the dendrites and on the axon, either, which were discussed to be due to a neurotoxic effect of amphetamine.

Amphetamine↗
PubMed1982

Preparation and characterization of subcellular fractions from the liver of the Northern Pike, Esox lucius.

The present study was designed to prepare and characterize subcellular fractions from the liver of the Northern pike (Esox lucius), with special emphasis on the preparation of microsomal fractions suitable for studying xenobiotic metabolism. The purity of the different fractions obtained by differential centrifugation, as well as the recovery of different organelles, was determined using both enzyme markers and morphological examination with the electron microscope. Attempts were also made to increase the recovery of fragments of the endoplasmic reticulum in the microsomal fraction. Finally, the subcellular distribution of several drug-metabolizing enzymes (cytochrome P-450, benzpyrene monoxygenase, epoxide hydrolase and glutathione transferases) were determined. With the exception of the subcellular distribution of epoxide hydrolase, the results obtained here resemble closely those reported fo rat liver and the microsomal fraction prepared is highly suitable for further studies of drug metabolism in pike liver.

Animals↗
PubMed1982

[Transmitter histochemistry of the olfactory tubercle in the rat].

The tuberculum olfactorium of the adult rat was investigated by means of neurohistological, fluorescence histochemical and enzyme histochemical methods. Using the rapid Golgi impregnation technique, seven neuron types could be demonstrated which can clearly be differentiated according to morphological criteria. Using the glyoxylic acid techniques, strongly fluorescent dopamine fibers are, in different densities, visible within the various laminae. Kainic acid application into the ventral tegmental area is followed by a strikingly reduced, no more structurally associated dopamine fiber fluorescence. After DFP intoxication, only a small proportion of the neuron population of the tuberculum olfactorium does exhibit an AChE activity; the AChE containing neurons are different as to their size and shape. The findings presented here are discussed with respect to the attributability of histochemical findings to cytoarchitectural features of this brain area.

Acetylcholinesterase↗
PubMed1982

Benzo(a)pyrene metabolism by rat liver microsomes: effects of adding purified glutathione S-transferases A, B, and C.

We have examined the effects of adding glutathione and isolated cytosolic glutathione S-transferases A, B, and C to rat liver microsomes metabolizing benzo(a)pyrene. Addition of glutathione alone resulted in the conjugation of 15 to 20% of the total metabolites of benzo(a)pyrene, and this conjugation could be inhibited almost entirely by bromosulfophthalein (an inhibitor of glutathione S-transferases), indicating that it is catalyzed by the glutathione S-transferase present in microsomes. Addition of purified cytosolic glutathione S-transferases A, B, and C yielded about 30 to 40% conjugate formation. Analysis of metabolites by high-pressure liquid chromatography demonstrated that the formation of 4,5-diol of benzo(a)pyrene was decreased by at least 80% by conjugation and that the 7,8-diol was also decreased significantly (40 to 60%). In addition, it was found that glutathione S-transferase B is capable of conjugating benzo(a)pyrene 1,6- and 3,6-quinones.

Animals↗
PubMed1982

Microsomal glutathione S-transferase. Purification, initial characterization and demonstration that it is not identical to the cytosolic glutathione S-transferases A, B and C.

Rat liver microsomal glutathione S-transferase was activated with N-ethylmaleimide, solubilized with Triton X-100, and purified by chromatography on hydroxyapatite and CM-Sepharose. A 36-fold purification resulted in a 36% yield, indicating that the glutathione S-transferase accounts for 2.5-3% of the original microsomal protein. The purified protein moved as a band with an apparent molecular weight of 14 000 on sodium dodecyl sulphate gel electrophoresis and appeared to be nearly homogeneous. The complex formed between the purified microsomal glutathione S-transferase and Triton X-100 has a sedimentation coefficient of 3.2 S, a partial specific volume of 0.844 cm3/g, and a Stokes radius of 5.5 nm. The complex has a molecular weight of 127 000 and contains three or four polypeptide chains and 112-134 detergent molecules. Antibodies directed against soluble glutathione S-transferases A, B and C do not react with the purified microsomal enzyme. This finding, together with differences in molecular weight and substrate specificity, demonstrate that the microsomal glutathione S-transferase is an enzyme distinct from the cytosolic glutathione S-transferases.

Animals↗
PubMed1981

Induction of drug-metabolizing systems and related enzymes with metabolites and structural analogues of stilbene.

trans-Stilbene oxide has been found to be a new type of inducer of drug-metabolizing systems. In order to identify the true inducer and to determine the structural requirements for induction, rats were treated with metabolites and structural analogues of stilbene. Subsequently, hepatic levels of cytochrome P-450, microsomal epoxide hydrolase, and cytoplasmic glutathione S-transferase were assayed. All three enzymes were induced by cis- and trans-stilbene and cis- and trans-stilbene oxide. In addition, epoxide hydrolase and glutathione S-transferase activities were induced by benzoin and benzil. In contrast, the diols and benzoic acid had little, if any, effect. The main conclusions drawn from these findings are that: (1) trans-stilbene oxide itself seems to be the inducer of drug-metabolizing enzymes; and (2) benzil is more selective as an inducer of epoxide hydrolase than is trans-stilbene oxide. Attempts to induce epoxide hydrolase with other structural analogues of stilbene led to the following conclusions: (1) two phenyl rings are required for induction; (2) the induction is not as great if the rings are substituted or one of the ring carbon atoms is replaced by a nitrogen; (3) a carbon bridge between the phenyl groups generally results in a greater induction, especially if the bridge contains an epoxy group or one or two keto groups.

Animals↗
PubMed1981

Computer-aided calculation of dose response curves in behavioral pharmacology by using a nonlinear regression procedure.

In a variety of behavioral pharmacological experiments drug induced graded responses can be recorded even if one animal can be tested only once. In this case the analysis of dose response relationships will be accompanied with theoretical and practical problems additional to those known for dose response curves in single subjects as well as for the all-or-none type of responses. An experimental design was considered where one quantitatively measurable response of each animal tested contributed to an average dose response relationship. Use was made of a four parameter model capable of fitting s-shaped dose response curves over the whole feasible dose range for solving this nonlinear regression problem. Two examples, the dose dependent increased locomotor activity induced by apomorphine and the inhibited locomotor activity after pimozide treatment, were given to demonstrate the use of the method described and to direct the reader's attention to the wide range of its possible applications.

Animals↗
PubMed1980

Induction of glutathione S-transferases A, B and C in rat liver cytosol by trans-stilbene oxide.

The cytoplasmic glutathione S-transferase activity of rat liver has been shown to increase to 300--400% of control values after treatment of the animals with trans-stilbene oxide and this phenomenon has been further characterized in the present study. Quantitative immunological determinations showed that the content of glutathione S-transferases A, B and C together constituted 4.5% of the soluble proteins in the hepatic cytoplasm of untreated rats. The content rose to 12.9 and 17.4% after treatment with trans-stilbene oxide or a combination of trans-stilbene oxide, 3-methylcholanthrene and phenobarbital, respectively. It was demonstrated that the cytosolic fraction from induced liver contains 4.2 times as much antigen which can be precipitated with antiglutathione S-transferase B antiserum as does control cytosol. Antiglutathione S-transferase C, which intereacts with transferases A and C, precipitates 3.3 times as much protein from the induced cytosol compared with control. Crossed immunoelectrophoresis and purification demonstrated that both A and C are increased in amount after treatment with trans-stilbene oxide. Thus, cytosolic glutathione S-transferases A, B, and C in liver are all induced by treatment of rats with trans-stilbene oxide. Immunological crossreaction, similar behavior during chromatography on CM-cellulose and hydroxyapatite and similar specific activities suggest that the control and induced enzymes are essentially identical, trans-Stilbene oxide was found to serve as a relatively poor second substrate for glutathione S-transferases A, B and C and can thus be said to cause substrate induction of these enzymes.

Animals↗
PubMed1980

Characterization of rat-liver microsomal glutathione S-transferase activity.

Rat liver microsomes were shown to catalyze the conjugation of 1-chloro-2,4-dinitrobenzene with glutathione and this activity has been characterized. It cannot be removed from the microsomes by washing or other procedures which release loosely bound material from membranes. The microsomal glutathione S-transferase can be activated up to eight fold by treatment with N-ethylmaleimide. This activation also affects the apparent Km of the enzyme(s) for both glutathione and 1-chloro-2,4-dinitrobenzene. Upon subcellular fractionation of the liver the N-ethylmaleimide-activateable glutathione S-transferase distributes in the same manner as a marker for the endoplasmic reticulum and unlike markers for the other organelles and for the cytoplasm. Treatment of microsomes with proteases revealed that the enzyme is at least partially exposed on the cytoplasmic surface of the endoplasmic reticulum. Finally, three inducers of drug-metabolizing systems-i.e. phenobarbital, methylcholanthrene, and trans-stilbene oxide-all increase the activity of the cytoplasmic glutathione S-transferases, but they do not affect the microsomal activity. These and other considerations indicate that the microsomal glutathione S-transferase(s) is distinct from the cytoplasmic enzymes catalyzing similar reactions. The microsomal enzyme is likely to be involved in drug metabolism and the possibility of activating it through attack on a sulfhydryl group may represent an important physiological response to certain xenobiotics.

Animals↗