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Biomedical subjects

J D Fernstrom

Publications and source records attributed to J D Fernstrom.

At least 73 records · Page 4Linked to original sources
PubMed1986

Effects of aspartame ingestion on the carbohydrate-induced rise in tryptophan hydroxylation rate in rat brain.

Effects of aspartame (aspartyl-phenylalanine-methylester) on increases in brain-tryptophan level and hydroxylation rate following a high-carbohydrate, protein-free meal were tested. After an overnight fast, rats consumed a protein-free meal containing one of several levels of aspartame. Blood and brain amino acid levels and the in vivo rate of tryptophan hydroxylation in brain were estimated at intervals thereafter. Ingestion of the meal alone increased brain-tryptophan level and hydroxylation rate. Aspartame did not modify these effects, except at doses of 530 mg/kg body weight or more. Results suggest a threshold dose of aspartame can be identified for the rat in single-meal studies above which suppression of carbohydrate-induced increases in brain-tryptophan level and serotonin synthesis occurs. This dose, however, is large and, when corrected for species differences in metabolic rate, is unlikely to be ingested by a human subject as a single load.

Administration, Oral↗
PubMed1986

In vivo inhibition of tyrosine uptake into rat retina by large neutral but not acidic amino acids.

The uptake of tyrosine into rat retina and brain was studied in vivo after its peripheral injection alone or in combination with other amino acids. Both retinal and brain tyrosine levels increased monotonically for at least 60 min after tyrosine administration. When tyrosine was injected along with branched-chain amino acids, but not with acidic amino acids, such increments in retinal and brain tyrosine levels were significantly attenuated. The postinjection tyrosine levels in retina and brain paralleled better the serum ratio of tyrosine to the sum of the other large neutral amino acids (which include the branched-chain amino acids) than the serum tyrosine level alone. These results suggest that tyrosine uptake into rat retina, like that into brain, is mediated by a competitive transport system shared among the large neutral amino acids.

Amino Acids↗
PubMed1986

Effects of cysteamine administration on the in vivo incorporation of [35S]cysteine into somatostatin-14, somatostatin-28, arginine vasopressin, and oxytocin in rat hypothalamus.

The effect of cysteamine injection on the in vivo incorporation of [35S]cysteine into somatostatin-14 (SRIF-14), SRIF-28, arginine vasopressin (AVP), and oxytocin (OXT) in rat hypothalamus was studied. [35S]Cysteine was injected into the third ventricle 1 h, 4 h, or 1 week after cysteamine (300 mg/kg, sc) injection; animals were killed 4 h later. The drug was found to substantially reduce immunoreactive SRIF levels, but not OXT or AVP, 4 h after its injection. Cysteamine also caused large reductions in label incorporation into SRIF-14, SRIF-28, and OXT 1 and 4 h after drug injection. However, [35S]cysteine incorporation into AVP was increased substantially at these time points, while that into acid-precipitable protein was normal. One week after cysteamine injection, label incorporation into all hypothalamic peptides was normal. Cysteine specific activity was also measured after [35S]cysteine injection and was found to be similar in treatment and control groups. The results suggest that cysteamine inhibits the syntheses of SRIF-14, SRIF-28, and OXT and stimulates that of AVP.

Animals↗
PubMed1985

Dietary effects on brain serotonin synthesis: relationship to appetite regulation.

This review summarizes evidence showing that: 1) the synthesis of serotonin in the brain depends directly on the amount of tryptophan available to it from the circulation; 2) tryptophan uptake into brain depends on the blood levels not only of tryptophan, but also of other aromatic and branched-chain amino acids that compete with tryptophan for a common transport carrier into brain; and 3) dietary factors that influence the blood levels of tryptophan and these other amino acids can modify tryptophan uptake into brain, and consequently the rate of serotonin formation. Additionally, data are reviewed that attempt to show that appetite for protein and/or carbohydrates is dependent on the relationship between food intake, plasma amino acid pattern, brain tryptophan uptake, and serotonin synthesis.

Amino Acids↗
PubMed1985

Absence of chronic effects of dietary protein content on brain tryptophan concentrations in rats.

Groups of young, adult, male rats were given free access for 2 wk to a diet containing 12, 24 or 40% protein (dry weight). During this period, all animals grew considerably; those consuming the 12% protein diet grew less rapidly than those ingesting the higher percent protein diets. At the end of 2 wk, six rats from each diet group were killed every 4 h throughout a 24-h period, and blood samples and whole brains were obtained for analysis. Serum tryptophan levels were lowest in animals consuming the 12% protein diet, intermediate in rats consuming the 24% protein diet and highest in rats consuming the 40% protein diet (at all times studied). Brain tryptophan levels, however, did not differ significantly as a function of dietary protein content. The ratio in serum of the concentration of tryptophan to the sum of the concentrations of its competitors for brain uptake also was not significantly influenced by dietary protein level. Levels of 5-hydroxyindoles in brain showed significant diurnal variations but no evidence of a significant effect of dietary protein content. Since the ratio of serum tryptophan to its competitors and the levels in brain of tryptophan and 5-hydroxyindoles did not vary as a function of dietary protein intake, the results do not support the view that these variables serve as signals to the brain for regulating long-term dietary protein intake.

Animals↗
PubMed1984

Caffeine injection raises brain tryptophan level, but does not stimulate the rate of serotonin synthesis in rat brain.

Acute caffeine injection (100 mg/kg) elevates brain levels of tryptophan (TRP), serotonin (5HT), and 5-hydroxyindoleacetic acid (5HIAA). Experiments were performed to determine if the increases in 5HT and 5HIAA result from a stimulation of the rate of 5HT synthesis. Both the rate of 5-hydroxytryptophan (5HTP) accumulation following NSD-1015 injection, and the rate of 3H-5-hydroxyindole synthesis from 3H-tryptophan were measured in vivo following caffeine administration and found to be normal. Tryptophan hydroxylase activity, as measured in vitro in brain homogenates, was also unaffected by caffeine. The results suggest that the elevations in brain 5HT and 5HIAA levels produced by caffeine do not reflect enhanced 5HT synthesis, despite significant elevations in brain TRP level. Some other mechanism(s) must therefore be responsible for these elevations in brain 5-hydroxyindole levels.

5-Hydroxytryptophan↗
PubMed1984

The effects of clonidine on EEG wavebands associated with sleep in the rat.

Clonidine was studied for its effects in rats on the occurrence of several EEG waves that characterize the sleep/waking cycle. Intraperitoneal administration of the drug (0.001-1.0 mg/kg) at the onset of the daily light period induced low frequency (4-7 Hz) rhythmical slow activity (RSA), and suppressed delta-wave occurrence. These effects were more prominent with increasing dose. Clonidine also had a biphasic effect on spindles: at low doses it suppressed, while at high doses it enhanced spindle occurrence. These effects could not be characterized as modifications in any of the classical sleep stages. A clearly non-classical state was induced by the clonidine in these studies. These results suggest that in rat, effects of clonidine cannot simply be interpreted as an alteration in one or more of the classically-defined sleep states.

Animals↗
PubMed1984

In vivo tyrosine hydroxylation in the diabetic rat retina: effect of tyrosine administration.

The in vivo rate of 3,4-dihydroxyphenylalanine (DOPA) accumulation was measured in light-adapted retinas of normal and diabetic albino rats. DOPA accumulation was significantly below normal in diabetic retinas; tyrosine levels were also reduced. In vitro tyrosine hydroxylase activity was normal. The administration of tyrosine methylester (500 mg/kg i.p.) to diabetic animals significantly raised retinal tyrosine levels and enhanced DOPA accumulation. Reduced tyrosine levels may therefore contribute to the observed reduction in in vivo tyrosine hydroxylation rate in the diabetic retina.

Animals↗
PubMed1984

Long term stability of rat sleep quantified by microcomputer analysis.

An inexpensive microcomputer system is described for the direct recording of electrographic data from animals. Using this system, electrographic data can be recorded continuously on a polygraph and simultaneously quantitated by the computer, for days or weeks. Our system quantifies the amounts of delta waves, spindle bursts, hippocampal RSA activity and movement spikes for 15 sec epochs. These electrographic data are stored by the computer and subsequently can be used to score sleep stages. We find that the computer reliably counts waves; using these data, it can then score sleep stages off-line with about 90% accuracy. With this system, we find that the minutes/hour of both SWS and REM are remarkably stable from day to day. The absolute number of delta waves, spindle bursts, trains of RSA and movement counts/hour also remain stable from day to day. This type of system should find significant application in situations where quantitation of longterm effects of drugs, diets and other environmental inputs on sleep states or EEG wave bands are of interest.

Animals↗
PubMed1983

Effects of acute and chronic trazodone administration on serum prolactin levels in adult female rats.

Trazodone was tested for its ability to elevate serum prolactin levels in mature female rats. When the drug was administered acutely to female rats at doses up to 80 mg/kg ip, it induced a clear rise in serum prolactin levels, with a minimum effective dose of 20 mg/kg; blood trazodone levels at these doses were between 1.6-2.4 micrograms/ml. However, trazodone could not be considered to be a potent stimulator of prolactin secretion, since the injection of haloperidol at 2 mg/kg elevated serum prolactin to values twice those seen in animals receiving the 80 mg/kg dose of trazodone. When trazodone was administered chronically in the diet for two or four weeks, at an average daily dose of 80 mg/kg, serum trazodone levels were found to be 100-200 ng/ml when measured at each stage of the estrous cycle. Serum prolactin levels in trazodone-treated animals, however, did not differ from those in control rats. Moreover, drug-treated animals showed normal proestrus surges in serum prolactin. The results of these studies thus indicate that acutely, at very high doses, trazodone probably can stimulate prolactin secretion modestly in female rats. However, when consumed chronically at 80 mg/kg/day, the drug has no effects on serum prolactin levels. Therefore, if trazodone stimulates prolactin secretion by altering neurotransmission across dopamine and/or serotonin synapses in brain, it is probably not potent in these actions, at least as concerns those dopamine and serotonin neurons that influence the secretion of prolactin.

Animals↗
PubMed1983

Acute effects of aspartame on large neutral amino acids and monoamines in rat brain.

The dipeptide aspartame (APM; aspartylphenylalanine methylester), an artificial sweetener, was studied in vivo for its ability to influence brain levels of the large neutral amino acids and the rates of hydroxylation of the aromatic amino acids. The administration by gavage of APM (200 mg/kg) caused large increments in blood and brain levels of phenylalanine and tyrosine by 60 minutes. Brain tryptophan level was occasionally reduced significantly, but the brain levels of the branched-chain amino acids were always unaffected. Smaller doses (50, 100 mg/kg) also raised blood and brain tyrosine and phenylalanine, but did not reduce brain tryptophan levels. At the highest dose (200 mg/kg), APM gavage caused an insignificant increase in dopa accumulation (after NSD-1015), and a modest reduction in 5-hydroxytryptophan accumulation. No changes in the brain levels of serotonin, 5-hydroxyindoleacetic acid, dopamine, dihydroxyphenylacetic acid, homovanillic acid, or norepinephrine were produced by APM administration (200 mg/kg). These results thus indicate that APM, even when administered in amounts that cause large increments in brain tyrosine and phenylalanine, produce minimal effects on the rates of formation of monoamine transmitters.

Amino Acids↗
PubMed1983

In vivo studies of somatostatin-14 and somatostatin-28 biosynthesis in rat hypothalamus.

The biosynthesis of somatostatin-14 (SRIF-14) and somatostatin-28 (SRIF-28) was studied in rat hypothalamus after injection of 35S-labeled cysteine into the third ventricle. Cysteine specific activity was quantitated, and found to decline rapidly after injection of the labeled amino acid: less than 0.1% of the injected label remained as free cysteine in the hypothalamus 30 min post injection. Incorporation of label into SRIF-14 and SRIF-28 reached maximum values 8 h post injection, compared with a labeling maximum at 1-2 h for acid-precipitable protein. Within 2 h after [35S]cysteine injection, nearly half of the total labeled hypothalamic SRIF appeared in the medial basal hypothalamus; 24-h post injection this percentage reached approximately 75%. Colchicine administration dramatically reduced the appearance of labeled SRIF in medial basal hypothalamus, but had no apparent effect on the total incorporation of [35S]cysteine into SRIF-14, SRIF-28, or acid-precipitable protein, or on radioimmunoassayable SRIF levels. These results suggest that 1) the technique employed for administering [35S] cysteine delivers the label as a pulse; 2) the timing of the appearance of labeled amino acid in SRIF-14, SRIF-28, and acid-precipitable protein is consistent with initial synthesis of a larger prohormone, followed by conversion to peptide products; and 3) the newly synthesized peptides are rapidly transported to the medial basal hypothalamus by a colchicine sensitive mechanism.

Animals↗
PubMed1983

Effect of experimental diabetes on the levels of aromatic and branched-chain amino acids in rat blood and brain.

Male rats treated 3 wk earlier with streptozotocin showed abnormally high blood levels of leucine, isoleucine, and valine throughout the 24-h period. Serum phenylalanine levels were slightly increased, while those of tryptophan and tyrosine were occasionally reduced. In brain, the level of each branched-chain amino acid was significantly increased above normal at all times. The brain concentration of each aromatic amino acid was always below normal. These changes were restored almost to normal by exogenous insulin therapy. Since the ingestion of protein is normally a major factor influencing blood amino acid levels, the effect of ingesting single, protein-containing meals on the blood and brain levels of these amino acids was also studied. After an overnight fast, the ingestion of a protein-containing meal by diabetic rats increased substantially both blood and brain levels of each branched-chain amino acid. No such increases occurred in normal rats. Ingestion of this meal produced only small changes in the brain and blood levels of the aromatic amino acids in both diabetic and normal rats. The changes in the brain level of each large neutral amino acid in some cases paralleled those in its blood level. More often, they paralleled the changes in the blood ratio of each amino acid to the sum of the other aromatic and branched-chain amino acids. This ratio is often a good predictor of the competitive transport of these amino acids into brain (Fernstrom and Faller, 1978). The observed changes in the brain levels of these amino acids in diabetes may influence the rates at which they are consumed in metabolic pathways within this organ.

Amino Acids↗
PubMed1982

Osmolal effects on vasopressin secretion in the streptozotocin-diabetic rat.

To determine the relationships between serum levels of arginine vasopressin (AVP) and serum osmolality and sodium in diabetic rats, we measured these variables in streptozotocin-diabetic and normal animals treated with water, isotonic saline, or hypertonic saline. Serum osmolality was higher and sodium lower in untreated diabetics than in controls; these variables increased in both groups after hypertonic saline. Serum AVP levels (measured by radioimmunoassay in Amberlite-extracted serum) were 2.3 +/- 0.5 and 9.8 +/- 1.7 pg/ml in control and diabetic rats, respectively, injected with isotonic saline. AFter injection of hypertonic saline, serum AVP levels rose to 14.5 +/- 2.3 pg/ml in controls and 18.7 +/- 1.7 pg/ml in diabetics. Water injection decreased serum AVP in diabetics (as in normals), but only to 5.8 +/- 1.0 pg/ml. To assess indirectly whether the chronically high levels of AVP in serum had an impact on kidney function, diabetic rats were studied after passive immunization with an anti-AVP serum. This treatment increased urine flow and decreased urine osmolality in dehydrated diabetic rats. Taken together, these data affirm in diabetic rats, as in humans, the occurrence of 1) elevated steady-state levels of AVP in serum; 2) abnormal sensitivity of AVP secretion to changes in serum sodium and osmolality; and 3) an apparently intact end-organ responsiveness to AVP.

Animals↗
PubMed1982

Studies on the antihypertensive action of L-tryptophan.

The administration of L-tryptophan to spontaneously hypertensive rats caused a dose-related decrease in blood pressure. Maximal reductions occurred 2 hr postinjection. This effect could be attenuated by 1) coadministration of valine, an amino acid that competes with tryptophan for brain uptake; 2) pretreatment with metergoline, a serotonin receptor antagonist; and 3) pretreatment with parachlorophenylalanine, which inactivates tryptophan hydroxylase. In contrast, the effect of tryptophan on blood pressure could be enhanced by pretreatment with fluoxetine, a drug which blocks serotonin reuptake into presynaptic terminals. Taken together, these results indicate that tryptophan injection lowers blood pressure by a mechanism involving increased tryptophan uptake into brain, followed by enhanced conversion of the amino acid to serotonin (not tryptamine) and, ultimately, increased release of serotonin by brain neurons. The data thus support the notion that serotonergic neurons in the rat brain function in circuits that lower blood pressure.

Amino Acids↗