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Biomedical subjects

G Huether

Publications and source records attributed to G Huether.

At least 55 records · Page 3Linked to original sources
PubMed1996

Serotonin transporters in the rat frontal cortex: lack of circadian rhythmicity but down-regulation by food restriction.

Molecular biological findings have indicated that the affinity and the density of presynaptic serotonin transporters may be subject to adaptive regulation, but the physiological conditions that may act to trigger such changes are presently unknown. By means of [3H]paroxetine binding to rat cortical membranes, we studied the influence of two physiological variables that are clearly associated with altered serotonergic activity--circadian rhythm and semistarvation--on K(D)and Bmax values of the serotonin transporter of the rat frontal cortex. No circadian fluctuations of both parameters were observed. Also, semistarvation (50% reduction of normal voluntary food intake) for 2 days had no effect on either K(D) or Bmax values of cortical [3H]paroxetine binding. Food restriction for either 7 days or 2 weeks, however, resulted in a significant, approximately 30%, reduction of the density of cortical serotonin transporters with unchanged transporter affinity. These findings indicate that long-term changes in the density of cortical serotonin transporters can be induced by long-lasting alterations of certain environmental variables. Because the duration and the radius of action of presynaptically released serotonin are governed by the efficiency of the reuptake mechanism, such adaptive changes of serotonin transporter density must be expected to cause long-term alterations of the modulatory impact of the central serotonin system on certain brain functions.

Animals↗
PubMed1996

Nocturnal melatonin secretion and sleep after doxepin administration in chronic primary insomnia.

Nocturnal melatonin secretion and polysomnographic sleep patterns were investigated in ten patients with chronic primary insomnia (age 41.3 +/- 9.5 years) and in five healthy subject, (age 27.2 +/- 0.7 years) after either a single intravenous administration of 25 mg doxepin or placebo in a randomized, double blind, and cross-over setting. In the patient group a third session was performed after a three-week open oral treatment with 25 mg doxepin daily. The single-dose administration of doxepin did not affect plasma melatonin concentrations in either the patients on the healthy subjects. After three weeks of oral doxepin intake by the patients, the area under the curve of total nocturnal plasma melatonin concentration was significantly increased by 26% and the peak values were increased by 30%. Both after the single i.v. treatment as well as after long-term oral administration, doxepin also significantly improved sleep latency, total sleep time, and sleep efficiency in the insomniacs as well as the healthy subjects, whereas the nocturnal wake time was decreased. These findings indicate that this tricyclic antidepressant not only improves sleep and but also preserves the secretion of a hormone which is believed to play a special role in the circadian sleep-wake rhythm. Long-term doxepin treatment of chronic insomniac patients not only improves sleep but also restores nocturnal melatonin secretion in these patients.

Adult↗
PubMed1996

Melatonin as an antiaging drug: between facts and fantasy.

This contribution makes an attempt to critically reassess the impressive career of melatonin from a stepchild of hormone research to a best-seller of drug marketing. Melatonin is an extremely interesting hormone. It is involved in the regulation of seasonal and circadian fluctuations of other hormones and in the synchronization of many different aspects of circadian rhythmicity to the light-dark cycle. In addition to these receptor-mediated functions, melatonin may act as a modulator of intracellular signal transduction to enhance or suppress the responses of many different cells to other incoming signals. Melatonin is also a potent scavenger of reactive oxygen species and may thus protect cells and tissues against radical-mediated damage. The production of melatonin declines with increasing age, and circulating melatonin levels are affected by certain pharmacological or physiological manipulations, notably food restriction which increases melatonin levels and prevents its age-related decline. Animal and cell culture experiments suggest that melatonin may have beneficial effects on certain aspects of aging and age-associated diseases. Of particular interest in this respect are reports on the influence of melatonin on the brain and the immune system. More research data are urgently needed in order to more clearly define the possible sites and mechanisms of these actions. Clinical studies need to be performed in order to identify possible side effects of long-term melatonin treatment, especially in elderly and diseased subjects. Serious concerns are raised about the use of uncontrolled, impure, or partially degraded melatonin preparations.

Aging↗
PubMed1996

[Psychological stress and neuronal plasticity. An expanded model of the stress reaction process as the basis for understand central nervous system adaptation processes].

A short survey on results and theories in psychosomatic and neurobiologic stress research is presented. Based on a comprehensive definition of the stress-reaction process, the biological and psychological consequences are described which are elicited by either controllable or uncontrollable stress. We conclude that controllable stress triggers the stabilization and facilitation of neuronal networks involved in the generation of appropriate patterns of appraisal and coping, whereas uncontrollable stress favours the extinction of inappropriate patterns and the reorganisation of neuronal connections underlying certain inappropriate behaviors. Both, controllable an uncontrollable stress-reaction-processes are therefore essential prerequisites of, and inherent challenges to, the development and adaptation of an individual in an ever changing external world but may also lead to psychodevelopmental failures and psychosomatic diseases.

Adaptation, Psychological↗
PubMed1995

Serotonin acts as a radical scavenger and is oxidized to a dimer during the respiratory burst of human mononuclear and polymorphonuclear phagocytes.

Isolated human mononuclear and polymorphonuclear phagocytes were stimulated in the presence and absence of serotonin (5-HT), the major secretory product of activated platelets, and the release of reactive oxygen metabolites during the respiratory burst was assessed by luminol-enhanced chemiluminescence. In the presence of 5-HT, a dose-dependent suppression of the chemiluminescence signal occurred, irrespective of the stimulus used to elicit the respiratory burst. A similar suppression of luminol-enhanced chemiluminescence was also seen in a radical generating cell free system. 5-HT was found to be oxidized by the reactive oxygen species released by stimulated phagocytes. This oxidation is prevented in the presence of other antioxidants. The major 5-HT oxidation product was isolated by gel chromatography and identified by mass-spectrometry as a 5-HT dimer, probably 5,5'-dihydroxy-4,4'-bitryptamine. It is concluded that the 5-HT released from activated thrombocytes at sites of inflammation and endothelial cell damage acts as a true scavenger of reactive oxygen species generated during the respiratory burst of stimulated phagocytes and may thus modulate various aspects of cell-mediated defence reactions.

Free Radical Scavengers↗
PubMed1995

Nocturnal plasma melatonin levels in patients suffering from chronic primary insomnia.

Polysomnographic sleep patterns and melatonin secretion were investigated in 10 patients (age: 41.3 +/- 9.5 years) who suffered from chronic primary insomnia and complained predominantly about difficulties in maintaining sleep and in five healthy controls (age 27.2 +/- 0.7 years). Nocturnal plasma melatonin concentrations were obtained hourly, measured by direct radioimmunoassay and statistically compared between insomniacs and controls with age as a covariate. Plasma melatonin levels in the patient group tended to begin increasing earlier in the evening and were significantly (P < or = 0.01) lower during the middle of the night (peak value 82.5 +/- 26.5 pg/ml) than in the healthy controls (peak value 116.8 +/- 13.5 pg/ml). Among the patients, the most severely reduced nocturnal plasma melatonin levels were found in those patients with a history of sleep disturbance lasting for longer than five years (N = 6; age 41.8 +/- 11.7 years; duration 15.3 +/- 5.9 years; peak value 72.1 +/- 25.0 pg/ml); whereas those chronic insomniacs affected for fewer than five years had relatively higher nocturnal levels (N = 4; age 40.6 +/- 6.5 years; duration 3.8 +/- 1.5 years; peak value 98.2 +/- 23.9 pg/ml). These results show that the circadian rhythm of melatonin secretion is disturbed in patients with chronic primary insomnia, and that the nocturnal plasma melatonin secretion is increasingly more affected the longer the patients are unable to maintain a regular sleep pattern.

Adult↗
PubMed1993

The contribution of extrapineal sites of melatonin synthesis to circulating melatonin levels in higher vertebrates.

While the production of melatonin in higher vertebrates occurs in other organs and tissues besides the pineal, the contribution of extrapineal sites of melatonin synthesis such as the retina, the Harderian glands and the gut to circulating melatonin levels is still a matter of debate. The amount of melatonin found in the gastrointestinal tract is much higher than in any other organ including the pineal and the gut appears to make a significant contribution to circulating melatonin at least under certain conditions. The gut has been identified to be the major source of the elevated plasma concentrations of melatonin seen after tryptophan administration and of the changes of circulating melatonin level induced by the feeding regimen. Whereas the circadian and circannual fluctuations of the concentration of melatonin in the blood seem to be triggered by changes of the photoenvironment and its effect of pineal melatonin formation, basal daytime melatonin levels and the extent of their elevation at nighttime appear to be additionally controlled by nutritional factors, such as the amount and the composition of ingested food and therefore availability of tryptophan as a rate-limiting precursor of melatonin formation by the enterochromaffin cells of the gastrointestinal tract.

Animals↗
PubMed1993

Effects of indirectly acting 5-HT receptor agonists on circulating melatonin levels in rats.

Because circulating melatonin levels are generally thought to be under the strict control of pineal N-acetyltransferase, little attention has been paid to the impact of an altered availability of serotonin (5-HT) on melatonin formation. In order to see whether melatonin synthesis is stimulated by an increased availability of free, cytosolic 5-HT, we studied the effects of 5-HT precursors, 5-HT releasers and reuptake inhibitors and of monoamine oxidase inhibitors, alone and in combination, on circulating melatonin levels in experimental animals. The administration of tryptophan and 5-HT-releasing drugs (fenfluramine, +/- 3,4-methylenedioxymethamphetamine) to rats caused a dose- and time-dependent elevation of circulating melatonin levels during the day and night. This increase in melatonin was further enhanced by inhibition of monoamine oxidase. The elevation of plasma melatonin caused by 5-HT-releasing drugs was prevented by prior administration of fluoxetine. Monoamine oxidase inhibitors and fluoxetine alone had no effect on circulating melatonin levels. These findings indicate that the administration of indirectly acting 5-HT receptor agonists which increase the free cytoplasmic pool of 5-HT may also elevate circulating melatonin levels. The results of this study suggest that the rate of pineal melatonin synthesis is dependent on the free cytoplasmic pool of 5-HT in pinealocytes and that the drug-induced elevation of this pool stimulates melatonin formation and increases circulating melatonin levels. At least some of the effects of indirectly acting 5-HT receptor agonists, e.g. on sleep, mood, food intake, pain perception, and neuroendocrine secretion, may therefore be mediated by the elevation of circulating melatonin and the subsequent activation of central melatonin receptors.

3,4-Methylenedioxyamphetamine↗
PubMed1993

Effect of transient reduction of cerebral blood flow in normotensive rats on striatal dopamine-release.

Bilateral Clamping of both Carotid Arteries (BCCA) in normotensive rats is known to cause a transient reduction in cerebral blood flow. Using in vivo trans-striatal microdialysis and HPLC/ECD we measured the release of dopamine and DA-metabolites under these oligemic conditions. BCCA caused a substantial stimulation of striatal DA-release (40-fold) and a decrease of the outflow of DA-metabolites. The elevated DA-release returned to baseline levels before the onset of reperfusion. Upon reperfusion, DA-metabolites rose above their initial baseline values. Trans-striatal administration of glutamate-diethylester (GDEE, 10 mM) attenuated the oligemia-induced DA-release. A sudden reduction of blood flow appears to disrupt the compartmentation of dopamine in striatal dopaminergic nerve endings in a similar but more moderate manner as compared to ischemia.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Administration of tryptophan-enriched diets to pregnant rats retards the development of the serotonergic system in their offspring.

It is well established that an increased availability of tryptophan stimulates serotonin synthesis not only in the adult but also in the developing brain. In order to study the influence of a permanently increased supply of tryptophan on the developing central 5-HT-system, female rats were fed a tryptophan-enriched diet from mating throughout pregnancy and lactation. The effect of this dietary regime was assessed by measurements of neurochemical markers of 5-HT innervation in the developing brain of their offspring. A diminished content of 5-HT, a decreased activity of tryptophan hydroxylase and a reduction of crude synaptosomal high-affinity 5-HT uptake was found in the cortex and in the brain stem of 5 day old rat pups of mothers fed the tryptophan-enriched diet. The postnatal increase of all three markers of serotonergic innervation in the offspring of these mothers was retarded. Both the initial depletion and the delayed maturation of 5-HT content, of tryptophan hydroxylase activity and of synaptosomal serotonin uptake were more pronounced in the cortex than in the brain stem. Apparently, the increased dietary intake of tryptophan throughout pregnancy and lactation caused a delayed outgrowth of 5-HT axons and/or reduced collateral sprouting and synapse formation in the brain of the developing offspring.

Animals↗
PubMed1992

Effect of tryptophan administration on circulating melatonin levels in chicks and rats: evidence for stimulation of melatonin synthesis and release in the gastrointestinal tract.

The administration of L-tryptophan (Trp, 150-300 mg/kg) to rats and chicks causes a rapid and dose-dependent elevation of circulating melatonin. The elevation of serum melatonin was greater after oral compared to the intraperitoneal route of administration of the same dose of Trp (150 mg/kg). The Trp-induced increase of circulating melatonin was unaffected by prior pinealectomy but was almost abolished by a partial ligature of the portal vein. The Trp-induced increase of melatonin in the portal blood preceded that in the systemic circulation. The gut contains considerable amounts of melatonin and the Trp-induced elevation of melatonin was greater in the duodenum compared to the pineal or the blood. The enterochromaffin cells of the gastrointestinal tract appear to be the major source of the Trp-induced increment of circulating melatonin. The possibility is discussed that the sedating, sleep inducing effects of Trp are mediated by the Trp-induced elevation of circulating melatonin.

Administration, Oral↗
PubMed1991

Changes in free amino acid concentrations in serum, brain, and CSF throughout embryogenesis.

Using the developing chick embryo as a model and a very sensitive micromethod for amino acid analysis, a complete analysis is presented of the developmental changes in free amino acid concentration in the blood, in the CSF, and in two different brain regions (optic lobe and frontal lobe) of the chick embryo (from day 4 of incubation, until day 5 post hatching). The developmental profile of Lys is the only one that is almost identical in all three compartments. The developmental profiles of the serum and of the brain are very similar for Arg and Phe, less so for Leu and Gly, and towards the end of the embryonic period, similar also for Val, Ile, Trp, and Met. The amino acid concentrations in the CSF are either much lower than in serum and brain already at the earliest stages, or they progressively decline to levels lower than those in brain and serum, most rapidly between day 6 and 8 of embryonic life. The concentrations of neuroactive amino acids (Gln, Glu, Asp, GABA, Tau, and Gly) in both brain regions begin to increase very early, and continue to rise, except Tau, which goes through a maximum at day 8. Comparative analysis of the developmental profiles of each amino acid in serum, brain, and CSF reveals that the blood supply and the cellular uptake, retention, and metabolism by neural cells are the major determinants of the free amino acid pool of the developing brain.

Amino Acids↗
PubMed1991

The influence of intravenous L-tryptophan on plasma melatonin and sleep in men.

The sleep-inducing mechanisms of L-Tryptophan (L-Trp) are generally thought to be mediated by a central serotonergic activation. Evidence is presented that some effects of L-Trp on sleep may be mediated by melatonin, a Trp-metabolite with sedative properties. Trp effects on vigilance, sleep, and plasma-melatonin concentrations were measured after double-blind application of 0, 1, 3, and 5 g L-Trp in nine and five healthy probands during daytime and nighttime, respectively. A significant sleep-inducing effect was observed after L-Trp administration during daytime and nighttime. The infusions of L-Trp caused a massive elevation of plasma melatonin levels. This effect was significant both during the night and the day, indicating that the increment of circulating melatonin may be of extrapineal origin.

Adult↗
PubMed1990

Role of prefeedings, plasma amino acid ratios and brain serotonin levels in carbohydrate and protein selection.

The relationship between carbohydrate and protein consumption and brain serotonin levels was investigated using Sprague-Dawley rats trained to press two levers. Each response on one lever was followed by a carbohydrate-rich 45-mg food pellet and each response on another lever was followed by a 45-mg pellet relatively high in protein. Access to the carbohydrate pellets immediately prior to the daily session depressed the number of carbohydrate pellets consumed but had little effect on the number of protein pellets consumed. Prior access to standard rat chow, which is relatively high in protein, had the opposite effect. Prior access to carbohydrates in solution did not affect pellet consumption. Plasma amino acid levels and brain serotonin levels were altered by intraperitoneal injections of insulin (2.4 U/kg) and tryptophan (40 mg/kg), but consumption of carbohydrate pellets relative to protein was not changed by these injections. Saline and glucose injections did not change relative consumption either. The results emphasize the importance of oral-sensory cues in food intake and selection but are not supportive of a major role for serotonin.

Amino Acids↗