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Biomedical subjects

W H Vogel

Publications and source records attributed to W H Vogel.

At least 19 recordsLinked to original sources

Effects of stress on amino acids and related compounds in various tissues of fasted rats.

The purpose of this study was to examine the effect of stress on the free amino acid pattern of plasma and various organs. Two groups of rats were deprived of food, for 24 hrs. One group was sacrificed after this time (fasting control representing mostly free endogenous amino acids) and the second group was first restrained in wire cages for 120 min before being sacrificed (fasting stress representing mostly the effects of stress on endogenous free amino acids). A third group had free access to food and was sacrificed at the same time (fed control representing mostly free amino acids absorbed from the gut and endogenous free amino acid metabolism). Fasting (as compared to fed controls) reduced alanine and arginine but increased ethanolamine, glutamic acid and glutamine in the plasma; increased ethanolamine, phosphoethanolamine and glutamic acid in the liver; increased carnosine, glutamic acid, phosphoethanolamine and glutamine in the ventricle; increased oxidized glutathione in the aorta; decreased alanine, aspartic acid, glutamic acid, leucine and methionine and increased glutamine in the pancreas; and decreased arginine in skeletal muscle. Fasting plus stress (as compared to fasting controls) reduced alanine and glutamine in the plasma; increased methionine in the liver; increased ethanolamine, GABA, and glutamic acid in the aorta; reduced arginine, glutamic acid, glutamine, leucine and methionine but increased ethanolamine in the ventricle; reduced ammonia and ethanolamine but increased histidine, isoleucine, leucine, lysine, phenylalanine, tyrosine and valine in the pancreas; and reduced ammonia in skeletal muscle. Fasting plus stress affects the amino acid composition of plasma and various of tissues but effects seen were individually different and strongly substance and tissue specific. Plasma changes did not coincide with tissue changes. Changes in the endogenous pattern of amino acids and related compounds in response to stress could be first indications of stress induced organ pathology.

Amino Acids

Serotonergic receptors modify the voluntary intake of alcohol and morphine but not of cocaine and nicotine by rats.

Effects of fluvoxamine, a relatively selective 5-HT uptake inhibitor, and ipsapirone, a relatively selective 5-HT1A agonist, were studied on the initiation and/or maintenance of the voluntary intake of alcohol, morphine, cocaine, and/or nicotine in rats using the two-bottle free-choice method. Fluvoxamine (30 mg/kg/day in the drinking fluid) when given during existing morphine consumption increased the intake of this drug (1 +/- 1 vs. 3 +/- 1 mg/kg/day) but had no effect on alcohol (2 +/- 2 vs. 2 +/- 2 g/kg/day) or cocaine (10 +/- 10 vs. 13 +/- 10 mg/kg/day) intake. Ipsapirone (10 mg/kg/day in the drinking fluid) when given during existing alcohol or morphine consumption decreased the intake of the first (2 +/- 2 vs. 1 +/- 1 g/kg/day) and increased the intake of the second drug (2 +/- 1 vs. 4 +/- 1 mg/kg/day), but had no effect on nicotine (1 +/- 1 vs. 1 +/- 1 mg/kg/day) or cocaine (7 +/- 8 vs. 7 +/- 6 mg/kg/day) intake. Ipsapirone when given before exposure to the above drugs reduced subsequent alcohol (2 +/- 1 vs. 1 +/- 1 g/kg/day) and increased subsequent morphine intake (2 +/- 2 vs. 4 +/- 1 mg/kg/day), but had no effect on the voluntary consumption of cocaine (8 +/- 7 vs. 10 +/- 6 mg/kg/day) and nicotine (1 +/- 1 vs. 1 +/- 1 mg/kg/day). These results suggest: (1) selective stimulation of 5-HT1A receptors reduces alcohol preference, (2) stimulation of all 5-HT receptors has no effect on alcohol intake, indicating the presence of inhibitory receptors, (3) stimulation of the serotonergic system in general stimulates morphine preference, (4) the serotonin system does not affect nicotine or cocaine preference and (5) the serotonergic system is not involved in the voluntary consumption of all, but-only of some drugs/chemicals of abuse. Recognition of these drug/chemical-specific sites in the brain might lead to a better understanding of differences in drug abuse patterns among humans and help in the development of specific drugs for the treatment of selective drug addictions.

Alcohol Drinking

Effects of L-DOPA/carbidopa administration on the levels of L-DOPA, other amino acids and related compounds in the plasma, brain and heart of the rat.

Rats were treated intraperitoneally with a mixture of 250 mg/kg L-DOPA and 40 mg/kg carbidopa or with vehicle and sacrificed 30 min later. Plasma, heart and cortex, midbrain, brainstem and cerebellum were removed from each animal and assayed by HPLC for L-DOPA and a large number of amino acids and related amino compounds. L-DOPA levels increased from undetectable (<0.2 nmol/ml or g) to 1,146, 1,007, 399, 376, 368 and 850 nmol/ml or g in the above tissues. In addition, several amino compounds were significantly affected by L-DOPA/carbidopa (p < or = 0.01). Plasma concentrations of phosphoserine, oxidized glutathione, citrulline, phenylalanine, tyrosine and 1-methylhistidine increased and arginine, glutamic acid and lysine decreased. In the heart, concentrations of phosphoserine, taurine, reduced glutathione, threonine, serine, glutamine, glycine, alanine, valine, GABA, ethanolamine, ammonia and arginine decreased. In the cortex, camosine and homocarnosine increased. In the midbrain, valine increased and leucine, ornithine and oxidized glutathione decreased. In the cerebellum, citrulline increased. In the brainstem, threonine, serine, asparagine, glutamine, oxidized glutathione, alanine, and leucine decreased. In the brainstem, arginine was slightly decreased with a concomitant increase in citrulline (p < 0.05), indicative of nitrous oxide formation. These results show that administration of L-DOPA/ carbidopa not only raises dopamine levels but can also affect other biochemicals and that the observed changes in amino acids and related compounds can perhaps contribute to the beneficial and/or adverse effects of L-DOPA/carbidopa therapy of Parkinson's disease.

Amino Acids

Levels of amino acids and related compounds in bronchoalveolar lavage fluids of asthmatic patients.

The constituents of bronchoalveolar lavage (BAL) fluid have been shown to reflect the presence and possible etiology of several pulmonary diseases. Presently, although research studies have reported the concentrations of cytokines and compounds such as major basic protein in BAL fluids, only the cellular elements, total protein, albumin, and immunoglobulins have been well defined. We hypothesize that amino acids and related amino compounds, well known participants in physiologic and biochemical processes, are present in BAL fluid and may have involvement in asthma. Our objective was to extend knowledge of the total chemical profile and clinical value of BAL fluids in humans by measuring these amino compounds in normal control subjects and asthmatic patients. Analysis by high-pressure liquid chromatography revealed the presence of 25 compounds. A few compounds in control subjects and patients were found to have values > 1.0 nmol/ml, while the majority were present in comparatively low concentrations < 1.0 nmol/ml. Asparagine, phosphoethanolamine, and taurine were significantly increased in the asthmatic patients. We conclude that the present profile of amino acids and related amino compounds in BAL fluid serves as a potential diagnostic tool in the study of various pulmonary disorders. The significance of increased asparagine, phosphoethanolamine, and taurine in the asthmatic patients is discussed and deserves further study.

Adult

Effect of repeated stress on a number of plasma amino acids and related compounds in young and old rats.

A number of amino compounds were studied in the plasma of young and old rats exposed to an immobilization stress on 3 different days. Baseline values were similar for all compounds between age groups except for slightly higher phenylalanine levels in old animals. Most differences were seen in the stress responses. Stress response intensities for alanine, aspartic acid, methionine, phenylalanine, and tyrosine were generally higher in old rats and recovery times from stress were usually longer. Although the stress responses decreased in young rats for some compounds over the three exposures, old rats showed no or less adaptation during this time. All the other amino acids showed no marked age effects. This study shows that certain plasma amino acids can serve as selective indicators of biological age and that their stress responses might be better markers of the aging process than their resting levels.

Age Factors

The effects of arginine administration on the levels of arginine, other amino acids and related amino compounds in the plasma, heart, aorta, vena cava, bronchi and pancreas of the rat.

Arginine (0.8g/kg, ip) or a vehicle was administered to rats and the levels of arginine and a large number of related amino compounds++ were measured in plasma, heart, aorta, vena cava, pancreas and bronchi at specified time intervals. Arginine levels (nmol/ml) increased in the plasma from 237 to 3172 at 15 min, 1236 at 30 min and 509 at 120 min. Peak concentrations (nmol/g) of arginine are reached in the tissues at 15 or 30 minutes with control and postinjection values of 500 and 1769 in the heart, 314 and 1563 in the aorta, 575 and 2976 in the vena cava, 760 and 1943 in the bronchi, and 234 and 3638 in the pancreas. Arginine injection also affects a number of amino acids and related compounds in the plasma and tissues most notably ornithine, isoleucine, phosphoserine, leucine and ethanolamine. However, plasma level changes do not predict tissue level changes which are highly specific for an individual compound and tissue. There was no general indication that arginine injection stimulates nitric oxide (NO) formation in any tissue. Thus, arginine is rapidly absorbed from the abdominal cavity into the blood stream, is quickly taken up by the tissues studied and disappears after about 2 to 3 hours. The effects seen after arginine administration could be caused by arginine per se and/or changes in one or more of the related amino compounds but not by NO.

Amino Acids

Levels of taurine, amino acids and related compounds in plasma, vena cava, aorta and heart of rats after taurine administration.

A pharmacokinetic study on the fate of administered taurine in blood and some tissues and the effects on other amino compounds is presented. Injection of taurine (0.8 g/kg i.p.) causes markedly elevated plasma levels (70-fold at 15 min) which decrease later and approach baseline values after about 4 h. Concomitantly, other plasma amino compounds such as ornithine, threonine, asparagine, glutamine, alanine, citrulline, tyrosine, tryptophan, glycine, ammonia and arginine are reduced, whereas beta-alanine and phosphoserine are increased. At 30 min, tissue levels of taurine are roughly doubled in the vena cava and heart and tripled in the aorta. Other amino compounds affected are aspartic acid, serine, valine, methionine, tyrosine, ammonia, lysine, histidine, and arginine in the vena cava; aspartic acid, reduced glutathione, serine, and ammonia in the aorta; and reduced glutathione, alanine, citrulline and methionine in the heart. In most of these cases, plasma changes do not predict tissue changes which are generally substance- and tissue-specific. Thus, pharmacological effects seen after taurine administration could be caused by elevated taurine levels per se and/or taurine-induced changes in some of the amino acids and related compounds.

Amino Acids

Effect of arginine administration on plasma and brain levels of arginine and various related amino compounds in the rat.

Arginine (ARG) was injected (0.8 g/kg, i.p.) into rats and levels of ARG were determined in plasma and four brain areas in the morning and afternoon. In control rats, brain values for ARG and some amino compounds are lower in the afternoon than in the morning. After ARG administration, ARG levels increase about 10-fold in the plasma and 2- to 3-fold in the brain areas. Brain ARG levels follow plasma levels. Elevated ARG levels affect a number of related amino compounds both in the plasma and all brain areas most notably ornithine, phosphoserine, glycine, GABA and ammonia. An increase of citrulline after ARG administration suggests the possibility of ARG-stimulated nitric oxide formation in the midbrain. Thus, ARG shows a daily rhythm in the plasma and brain and its administration increases ARG brain levels which seem to follow plasma levels. In addition, ARG alters a number of other amino compounds most notably GABA, glycine, ornithine and ammonia, indicating that some pharmacological effects seen after ARG administration might be caused by elevated levels of ARG and/or changes in other amino compounds.

Amino Acids

Effect of stress on amino acids and related compounds in various tissues of the rat.

The composition of various amino acids and related compounds in the aorta, ventricle, atria, liver, kidney, pancreas, bronchi and adrenals of rats is presented. These patterns are qualitatively similar, but quantitatively different. Stress changed these patterns. In the aorta, alpha-aminobutyric acid and ammonia are decreased. In the ventricle, phosphoserine and red. Glutathione are increased; and ammonia, arginine, asparagine, carnosine, ethanolamine, glutamic acid, glutamine, lysine, phosphoethanolamine and taurine are decreased. In the atria, alpha-aminobutyric acid, aspartic acid, ethanolamine and red. glutathione are increased; and ammonia is decreased. In the liver, alpha-aminobutyric acid, cystine, isoleucine, red. glutathione, methionine and phenylalanine are increased. In the kidney, ethanolamine is increased; and beta - aminobutyric acid, citrulline, cystathionine, glutamic acid, glycine and tryptophan are decreased. In the pancreas, alpha-aminoadipic acid, ox. glutathione, leucine, glutamine, 1-methylhistidine, phenylalanine, phosphoserine, tryptophan and valine are increased; and ammonia, cystine and aspartic acid are decreased. In the adrenal glands, anserine, glutamic acid, glutamine and ox. glutathione are increased; and arginine is decreased. In the bronchi, ethanolamine and beta-alanine are increased and alpha-aminobutyric acid and ox. glutathione are decreased. Thus, stress affects certain amino compounds but changes are substance and tissue specific and independent of changes seen in the plasma.

Amino Acids

The effect of acute and chronic diazepam treatment on stress-induced changes in cortical dopamine in the rat.

The mesocortical dopamine system is thought to play an important role in the etiology of the stress response. Dopamine (DA) has been shown to accumulate in the rat frontal cortex in response to a wide variety of stressors. Diazepam, an anxiolytic benzodiazepine, can reverse the effects of stress on cortical DA. We investigated the effects of acute and chronic diazepam administration on immobilization stress-induced changes of the DA system in the frontal cortex of the rat. In the first study, 2.5 mg/kg diazepam was administered 20 min prior to 40 min of immobilization stress. Acute diazepam significantly reduced basal levels of extracellular DA and antagonized the stress-induced increase in cortical DA when compared to untreated stressed rats. Acute diazepam did not significantly effect extracellular DOPAC. In the second study, an experimental group of rats was given approximately 2 mg/kg/day diazepam in their drinking water for 3 weeks. This treatment significantly reduced anxiety as assessed by a staircase test for anxiety. Chronic diazepam had no effect on basal levels of cortical DA. However, chronic diazepam treatment also attenuated stress-induced increases in extracellular DA when compared to untreated stressed control rats. Chronic diazepam did not affect stress-induced changes in DOPAC but it did antagonize the effects of stress on HVA. Thus, acute and chronic diazepam treatment can antagonize stress-induced activation of the mesocortical DA system. It is proposed that this effect is produced through an enhancement of GABAergic neurotransmission by diazepam. The role of the dopaminergic system during stress, anxiety, and schizophrenia is discussed.

3,4-Dihydroxyphenylacetic Acid

Effects of selective serotonergic agonists on aggressive behavior in rats.

The effects of the relatively specific serotonergic agonists 8-OH-DPAT (5-HT1A), TFMPP (5-HT1B), and DOB (5-HT2) were studied on defensive aggressive behavior in rats using the water competition test, 8-OH-DPAT (up to 0.25 mg/kg) and TFMPP (up to 1 mg/kg) were found to be ineffective, whereas DOB (up to 0.4 mg/kg) significantly reduced aggressive behavior in this test as well as in the offensive aggression test of the resident-intruder model. These results, combined with those from other studies, suggest that stimulation of 5-HT1A, 5-HT1B, and 5-HT2 receptors reduces offensive aggression, whereas defensive aggression is only decreased by 5-HT2 stimulation.

Aggression

Impact of stress and triiodothyronine on plasma magnesium fractions.

The differential regulation of free and bound plasma magnesium was studied in healthy volunteers exposed to various forms of stress, and patients screened for thyroid disorder. Both ergometric (7 min) and psychological (45 min) stress had no effect on free plasma magnesium, but increased the bound fraction. Before combined physical and psychological stress (45 min aerobatics) there was no correlation between the plasma fractions of magnesium; thereafter, there was a strong negative correlation between increased free and decreased bound magnesium. Three days of training in ground combat increased significantly the plasma levels of both magnesium fractions. Patients screened for thyroid disorder had a significant, positive correlation between both plasma fractions of magnesium, and a highly significant negative correlation between plasma T3 and the two magnesium fractions. No clear correlation between plasma catecholamines and magnesium levels was seen under any of the above conditions. Overall, the data show that the evaluation of the functions of circulating magnesium requires the specific measurement of the free and bound fractions.

Austria

Quantitative trait loci mapping of three loci controlling morphine preference using inbred mouse strains.

Quantitative trait loci mapping was used to identify the chromosomal location of genes which contribute to oral morphine preference (in a two-bottle choice paradigm) of C57BL/6J mice, compared to DBA/2J mice. An F2 intercross of these two strains (606 mice) was phenotyped for morphine preference and those mice demonstrating extreme values for morphine consumption (the highest and lowest 7.7%) were genotyped for 157 murine microsatellite polymorphisms. Maximum likelihood methods revealed three loci on murine chromosomes 1, 6 and 10 which are responsible for nearly 85% of the genetic variance observed between the two parental strains.

Animals

A study of oral morphine preference in inbred mouse strains.

C57BL/6J mice, in two-bottle choice paradigms, show increased oral morphine consumption, compared with DBA/2J mice. To determine whether this C57 morphine preference reflects differences in the receptor-mediated, reward-based action of morphine (as opposed to pharmacokinetic or gustatory differences), three experiments were performed. Consistent with previous two-bottle choice experiments, C57 mean (+/- S.D.) morphine consumption was 18 +/- 3 mg/kg/day, while the DBA mice consumed 1.4 +/- 1.2 mg/kg/day. Intraperitoneal naltrexone produced a 50% decrease in C57 morphine consumption (p < 0.01), while DBA mice showed no change. Consumption of fluid from the control bottle was not changed for either strain. Fifteen and 30 min after oral consumption of a morphine solution, plasma levels of morphine and its glucuronide derivative were not different between these two strains. C57 mice maintained a daily morphine intake of approximately 20 mg/kg across morphine concentrations of 0.05-0.4 mg/ml. These experiments suggest that the difference in oral morphine preference between C57 and DBA mice represents a reward-based mechanism which is mediated through opiate receptors.

Animals

Maudsley reactive and non-reactive rats differ in exploratory behavior but not in learning.

The Maudsley reactive (MR) and Maudsley non-reactive (MNR) inbred rat strains were created as an animal model of anxiety, based on open field behavior. We wished to determine whether previously described characteristic open field behavior and learning deficits in conditioned avoidance could be generalized to other paradigms of exploratory behavior (such as the staircase test) and learning (such as the T-maze swim test). As with other open field paradigms, the MR rats showed stable and large differences in the staircase test, compared with the MNR rats. In contrast, large and stable learning differences in conditioned avoidance and T-maze swim tests were not observed. We conclude that the MR rats exhibit exploratory behavior that is inhibited in a wide variety of paradigms, but learning deficits are not major characteristics of the phenotype. The inhibited exploratory behavior is a stable characteristic with large inter-strain differences, making measures of open field behavior suitable for quantitative trait loci analysis to determine the genes which explain these large and stable strain differences. Identification of these genes could provide clues to the genetic origins of some human anxiety disorders.

Animals

Aging and temporal discrimination of brief auditory intervals.

In a duration-discrimination experiment, young adults (mean age = 25.1), middle-aged adults (mean age = 45.5), and older adults (mean age = 64.6) were presented with two very brief auditorily marked intervals per trial, and their task was to decide which of the two was longer in duration. An adaptive psychophysical procedure was used to determine difference thresholds in relation to a constant standard interval of 50 ms. It was found that duration-discrimination performance was unaffected by age; all three age groups yielded a difference threshold of approximately 17 ms. It was concluded that the ability to discriminate durations of very brief auditory intervals appears to be based on an underlying timing mechanism that does not slow down with advancing adult age.

Adult

Detection and evaluation of persisting stress-induced hormonal disturbances by a post stress provocation test in humans.

Eighteen healthy army officers were subjected after prolonged rest to exhaustive ergometric work for about 15 minutes. Before and afterwards blood was taken from the cannulated antecubital vein for determination of free and sulfoconjugated catecholamines, cortisol, glucose, and white blood cell count. One week later, the same procedure was repeated with the same subjects with the difference that the probands underwent about 2.5 hours of difficult mountain climbing and a subsequent rest of 1.5 hours before ergometry. The most important results were: 1) total and bound fractions of catecholamines showed some significant differences between the first and second ergometry due to the previous mountain climbing stress; 2) serum cortisol did not increase after the first ergometry but did so significantly after the second ergometry due to the previous stress; low cortisol is not always indicative of the absence of stress; 3) the absolute number of white blood cells increased in both situations, correlated significantly with the severity of the stress and the individual increases were more person than situation specific and; 4) blood glucose remained unaffected in both situations. We conclude that a previous stress experience can affect a second stress response and that such a post stress provocation test can uncover persistent hormonal alterations. This procedure may be useful for the evaluation of inaccessible stress situations from subsequent stress measures.

Adult