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Biomedical subjects

J Engel

Publications and source records attributed to J Engel.

At least 685 records · Page 38Linked to original sources

The effect of long-term ethanol treatment on the sensitivity of the dopamine receptors in the nucleus accumbens.

The effect of local application of dopamine into the nucleus accumbens on locomotor activity was studied in rats during and after withdrawal of long-term ethanol treatment. The bilateral application of dopamine into the nucleus accumbens of both the ethanol and withdrawal rats produced a pronounced increase in coordinated locomotor activity, which was 8-10 times higher than that of untreated water control rats. This effect of dopamine was antagonized by intraperitoneally administered haloperidol indicating a specific effect on dopamine receptors. It is concluded that prolonged ethanol administration may produce an increased sensitivity of the dopamine receptors in the nucleus accumbens and further support the contention that central catecholamine mechanisms are involved in the mediation of the withdrawal syndrome observed after long-term treatment with ethanol.

Animals↗

Ontogenetic development of locomotor activity and rate of tyrosine hydroxylation.

A combined biochemical and behavioral study was performed postnatally on albino rats. An almost linear increase in total motor activity was observed from 1 to 15 days of age followed by a pronounced decrease in motor activity between days 15 and 18. The in vivo rate of tyrosine hydroxylase activity in whole brain was estimated by means of measuring accumulation of L-3,4-dihydroxyphenylalanine (Dopa) after administration of an inhibitor of aromatic amino acid decarboxylase NSD 1015. Additionally, Dopa accumulation was studied in regional brain areas in 10 and 14-day-old animals. A slight gradual increase in the amount of Dopa accumulation in whole brain was observed from 1 to 10 days of age, followed by a pronounced increase between 10 and 14 days. Regional studies revealed that the increase in Dopa accumulation was primarily located to striatum. The data suggest an involvement of central catecholamine neurons possibly dopaminergic, terminating in striatum. The decrease in motor activity observed after 15 days of age is interpreted as involvement of maturing inhibitory pathways of noncatecholaminergic origin.

Animals↗

Normalization by antipsychotic drugs of biochemically induced abnormal behavior in rats.

Male rats were trained to perform a conditioned avoidance response combined with a successive discrimination in a modified shuttle box. The administration of L-Dopa, 100 mg/kg i.p., after inhibition of peripheral aromatic amino acid decarboxylase, or apomorphine, 2 mg/kg i.p., was found to disrupt the discriminative but not the avoidance behavior. The dopamine receptor antagonist pimozide (0.5 mg/kg i.p.), but not the noradrenaline receptor antagonist phenoxybenzamine (10 or 20 mg/kg i.p.) completely antagonized the L-Dopa-induced abnormal behavior, indicating sn involvement of central dopamine mechanisms. The present data show that antipsychotic drugs not only inhibit behavior but can also improve behavior in animals with a disturbed function.

Animals↗

Suppression of ethanol-induced locomotor stimulation by GABA-like drugs.

Ethanol (2.4 g/kg) was given intraperitoneally to mice and was found to cause a marked increase in spontaneous locomotor activity. When mice were pretreated with low doses of agents which mimic or augment the action of GABA (gamma-hydroxybutyric acid, baclophen, or aminooxyacetic acid) the ethanol-induced locomotor stimulation was completely eliminated; Baclophen (10 mg/kg) was found to cause an initial increase followed by a later decrease in synthesis of catecholamines, as measured by the accumulation of dopa after inhibition of central aromatic L-amino acid decarboxylase, in dopamine-rich areas of rat brain. These data are consistent with previous findings that baclophen, as well as other agents which enhance the activity of GABA systems, reduce the firing of dopamine neurons, thus causing enhanced synthesis of dopamine via feedback mechanisms. These findings also indicate a potential interaction between GABA-like drugs and alcohol in man, and may be of heuristic value in the treatment of chronic alcoholism. The possibility that the mechanism of the inhibition of ethanol-induced locomotor stimulation by GABA-like drugs may be due to a selective interference with ethanol-induced dopamine release is discussed.

Aminobutyrates↗

Stimulation of mounting behavior but not lordosis behavior in ovariectomized female rats by p-chlorophenylalanine.

Treatment with 126 mg/kg of the 5-hydroxytryptamine synthesis inhibitor p-chlorophenylalanine (PCPA) for 3 days or daily treatment with 40 mg/kg of PCPA stimulated the display of mounting behavior, including ejaculatory patterns, by ovariactomized hormonally untreated female rats. PCPA treatment failed to induce lordosis behavior and did not affect the induction of lordosis behavior by daily injections of 2.0 mug/kg estradiol benzoate. These results show that mounting and lordosis behavior can be dissociated and it is suggested that these two sexual behavior patterns may be regulated by different neurotransmission mechanisms.

Animals↗

Extrinsic signals for monitoring the association reaction of proteins as introduced by fluorescent and non-fluorescent labels.

Two known dansyl labels (I, II) and 5-[2-(iodoacetamido)ethylamino]-1-naphthalene-sulfonic acid (III) and three new azo-dyes (IV - VI) were covalently attached to alpha-chymotrypsin and to basic pancreatic trypsin inhibitor by four different reactive groups. In order to protect the contact region of the proteins the complex of the two proteins was labeled. Advantage was taken of the fact that a group which is buried in the complex reacts about (see article) times slower than a group which is always exposed (K = dissociation equilibrium constant, [C] = concentration of the complex). The complex was dissociated at pH 3 and the labeled proteins were isolated by column chromatography. They were fully active. The dansyl label was immobilized when introduced by dansyl chloride but highly mobile when attached via the longer imidoester group (II). Changes of absorption and of fluorescence which occur when differently labeled reaction partners recombine were studied. Changes in absorption (up to 18%) were mainly due to interactions of the label of one protein with the other protein. Fluorescence changes of up to 480% could be obtained. They were interpreted in terms of a Förster type energy transfer between donor and acceptor labels and changes of absorption and quantum yield due to interactions of the labels with the proteins. The kinetic constants of complex formation are not seriously altered by the labels (Bösterling, B & Engel, J. (1976) this J. 357, 1297-1307, succeeding). It is concluded that the labeling technique may be of general value for kinetic and equilibrium studies of protein associations.

Affinity Labels↗

Influence of various fluorescent and non-fluorescent labels on the kinetics of the complex formation of alpha-chymotrypsin with basic pancreatic trypsin inhibitor (Kunitz).

The association of alpha-chymotrypsin with basic pancreatic trypsin inhibitor was studied using extrinsic signals produced by fluorescent and nonfluorescent labels. The reactive dyes were covalently bound to the proteins in the complexed state, in which the binding region was protected. The signals were sufficiently large to measure the complex formation at protein concentrations of 10(-9)M by fluorescence and down to 10(-6)M by absorption. Therefore, the association and dissociation could be followed over a broad range of concentration. Good correspondence was observed between data which were obtained with different labels and with published values for the unlabeled proteins. Existing differences could be explained by different buffer conditions used by the different authors. Also the pH dependence of the dissociation rate constants was essentially unaltered by the introduction of the labels. The large signals allowed a direct measurement of the equilibrium constants of dissociation, even at high pH, at which they are in the range of 10(-8)M. The experimentally determined binding constants were in agreement with those calculated from the rate constants. The temperature dependence of the binding constants revealed a small positive and pH-dependent enthalpy change [deltaHo = 4.0 kcal/mol (16.7 kJ) at H 7.0[. The results prove that the labeling can be performed in such a way that the equilibrium and kinetic parameters of the system studied are not significantly influenced.

Affinity Labels↗

Thermography as a diagnostic aid in tennis elbow.

Thermal screening was used in order to distinguish between Tennis Elbow and entrapment of posterior interosseous nerve. Both conditions have a very similar clinical picture but there should be an altogether different approach concerning treatment. The differential diagnosis is therefore of great importance and thermography of the elbow is a valuable aid in this distinction.

Athletic Injuries↗

The effect of long-term penfluridol treatment on the sensitivity of the dopamine receptors in the nucleus accumbens and in the corpus striatum.

The effect of local application of dopamine to the nucleus accumbens or corpus striatum on locomotor activity was studied in rats 4 days after withdrawal from a 6 weeks term of penfluridol medication. The bilateral application of dopamine into the nucleus accumbens of penfluridol-treated rats produced a very marked increase in coordinated locomotor activity which was 3-5 times higher than that of rats not treated with penfluridol. This effect of dopamine in both penfluridol-treated and control rats was antagonized by intraperitoneally administered haloperidol. The bilateral application of dopamine into the corpus striatum of penfluridol-treated animals produced a marked stereotyped behavioural syndrome in all rats studied, whereas no signs of stereotyped behaviour were observed in any of the rats not treated with penfluridol. The results indicate that long-term treatment of rats with the dopamine receptor blocking agent penfluridol produces an increase in the sensitivity of the dopamine receptors in the nucleus accumbens and corpus striatum and that the nucleus accumbens may play a role in locomotor activity.

Animals↗

The kinetics of the exchange of G-actin-bound 1: N6-ethenoadenosine 5'-triphosphate with ATP as followed by fluorescence.

1: N6-Ethenoadenosine 5'-triphosphate (epsilonATP), a fluorescent analog of ATP, binds to monomeric actin with a binding constant which is only about 5 times smaller than that of ATP. The spectroscopic changes which occur when epsilonATP binds to actin are studied and used to monitor the kinetics of nucleotide exchange. The first-order rate constant which is measured at a large excess of ATP over epsilonATP strongly depends on the ATP and Ca+ concentrations. This finding is explained by a mechanism in which the nucleotide dissociates much more easily from Ca2+-free than from Ca2+-bound actin. Of special interest is the temperature dependence of the dissociation rate constant. The Arrhenius plot shows a sharp bend near 24 degrees C.

Actins↗

Piribedil in Parkinson's syndrome: a clinical study.

The effect of a new dopamine receptor stimulating agent, piribedil (ET 495), was studied in 10 patients with Parkinson's syndrome, who had had no or a poor response to previous L-DOPA treatment, or had displayed marked side effects during L-DOPA administration. Piribedil produced significant improvement of the functions of activity of daily living (ADL), and appeared to have a preferential effect on parkinsonian tremor. However, treatment was difficult to control primarily because of severe psychiatric side effects.

Activities of Daily Living↗