Biogenic Amine Precursors Research Articles

Free Amino Acids in Dark‐ and White‐muscle Fish as Determined by O‐phthaldialdehyde Precolumn Derivatization

ABSTRACT: Free amino acids in fish reflect microbial spoilage, and are precursors of biogenic amines, factors of health concern and indicators offish decomposition. The objective of this research was to quantify levels of free histidine, lysine, ornithine and glutamine, which may become originators of highly undesirable histamine, cadaverine and putrescine in fish tissue. Liquid chromatography using o‐phthaldialdehyde (OPA) pre‐column derivatization, gradient elution and a C18 column were used for separation. Histidine was higher in white tissue of mahi‐mahi and tuna than in red tissue. No significant difference in lysine levels was found between the two tissues of tuna. Glutamine and ornithine were higher in red tissue of mahi‐mahi and tuna. Red snapper had higher levels of lysine than histidine.

Effects of dietary precursors to biogenic amines on the behavioural response from groups of caged worker honey bees (Apis mellifera) to the alarm pheromone component isopentyl acetate

SummaryThe sound or ‘buzzing response’ from groups of fifteen worker honey bees, Apis mellifera L., to the presentation of isopentyl acetate, an alarm pheromone component, was recorded through a microphone connected via a digital–analogue converter into a computer. The effects of ingested biogenic amine precursors 5‐hydroxytryptophan, L‐DOPA and tryptophan were tested on three variables measurable from the sound traces: onset of the buzzing response after presentation of the pheromone stimulus, the duration of the buzzing event, and the maximal sound frequency produced during the buzzing event. Bees fed high doses of 5‐hydroxytrytophan were found to react significantly more slowly and with a significantly lower maximum frequency than bees that were only fed sucrose controls. Bees fed DOPA were no different from controls for any of the variables measured, and bees fed tryptophan were so hyperactive that reliable responses to the presentation of alarm pheromone could not be made. Finally, the brains of worker bees fed these different precursors were examined for content of various neurochemicals. Bees fed 5‐hydroxytryptophan were found to have dose‐dependent elevations of both 5‐hydroxytryptophan and serotonin within their brains. Bees fed tryptophan were found to have dose‐dependent elevations of tryptophan and kynurenine in the brain but no change in brain serotonin. Bees fed DOPA had dose‐dependent increases in DOPA and dopamine levels within their brains. These results suggest that the hyperactive condition results from kynurenine metabolism, and the reduced response to alarm pheromone is related to serotonin metabolism.

The trace amine tyramine is essential for sensitization to cocaine in Drosophila

Background: Sensitization to psychostimulant drugs of abuse is thought to be an important aspect of human addiction, yet how it develops is still unclear. The development of sensitization to cocaine in the fruit fly Drosophila melanogaster is strikingly similar to that observed in vertebrates. By taking advantage of the powerful genetic approaches that are possible in Drosophila, we are able to identify and characterize mutants that fail to develop sensitization.Results: We found that the Drosophila mutant inactive (iav) failed to become sensitized to cocaine. Mutant flies had reduced amounts of the trace amine tyramine in the brain because of reduced activity of the enzyme tyrosine decarboxylase (TDC), which converts tyrosine to tyramine. Furthermore, cocaine exposure induced TDC enzyme activity in a time-dependent manner that paralleled the development of behavioral sensitization. The sensitization failure of iav flies could be rescued by feeding the flies with tyramine; other biogenic amines or amine precursors did not have the same effect.Conclusions: These results indicate an essential role for tyramine in cocaine sensitization in Drosophila.

Modulation of gastrin processing by vesicular monoamine transporter type 1 (VMAT1) in rat gastrin cells.

1. Gastrointestinal endocrine cells produce biogenic amines which are transported into secretory vesicles by one of two proton-amine exchangers, vesicular monoamine transporters type 1 and 2 (VMAT1 and 2). We report here the presence of VMAT1 in rat gastrin (G) cells and the relevance of VMAT1 function for the modulation of progastrin processing by biogenic and dietary amines. 2. In immunocytochemical studies VMAT1, but not VMAT2, was localized to subpopulations of G cells and enterochromaffin (EC) cells; neither was found in antral D cells. The expression of VMAT1 in antral mucosa was confirmed by Northern blot analysis, which revealed an mRNA band of approximately 3.2 kb, and by Western blot analysis, which revealed a major protein of 55 kDa. 3. In pulse-chase labelling experiments, the conversion of the amidated gastrin G34 to G17 was inhibited by biogenic amine precursors (L-DOPA and 5-hydroxytryptophan). This inhibition was stereospecific and sensitive to reserpine (50 nM), which blocks VMAT1 and VMAT2, but resistant to tetrabenazine, which is a selective inhibitor of VMAT2. 4. Dietary amines such as tyramine and tryptamine also inhibited G34 cleavage. This effect was associated with a loss of the electron-dense core of G cell secretory vesicles. It was not stereospecific or reserpine sensitive, but was correlated with hydrophobicity. 5. Thus rat antral G cells can express VMAT1; transport of biogenic amines into secretory vesicles by VMAT1 is associated with inhibition of G34 cleavage, perhaps by raising intravesicular pH. Dietary amines also modulate cleavage of progastrin-derived peptides, but do so by a VMAT1-independent mechanism; they may act as weak bases that passively permeate secretory vesicle membranes and raise intravesicular pH.

Novel form of L-aromatic amino acid decarboxylase mRNA in rat antral mucosa.

Gut endocrine cells possess the capacity to take up and decarboxylate biogenic amine precursors. Decarboxylation is mediated by aromatic L-amino acid decarboxylase (AADC) which is encoded by mRNAs differing in their 5' untranslated regions (UTR) depending on the usage of alternative first exons, 1a and 1b, each with its own acceptor site (-13 and -8 bases relative to the translation start site, respectively). We describe here a novel splice variant of exon 1a-AADC mRNA in rat antral mucosa. Both exon 1a and 1b mRNAs were expressed in rat antral mucosa, but the 1a form was spliced into the acceptor site usually associated with exon 1b (-8). An enteroendocrine cell line (STC-1) expressed exon 1a or exon 1b mRNAs spliced into the -8 acceptor site of exon 2. Transient transfection of a range of cell lines with reporter constructs revealed that all three 5' UTRs efficiently supported expression of the Luciferase reporter. There is therefore a novel, functional 5' UTR of AADC mRNA in rat antral mucosa; alternative AADC splice variants could provide the capacity for control at the level of mRNA translation.

EFFECTS OF ANTICONVULSANT TREATMENT AND LOW LEVELS OF FOLATE AND THIAMINE ON AMINE METABOLITES IN CEREBROSPINAL FLUID

A total of 157 epileptic patients were studied with respect to (1) biogenic amine precursors and metabolites in the CSF, (2) levels of folate and thiamine in the blood and CSF, (3) length of treatment with phenytoin (PHT), (4) PHT intoxication, (5) CNS atrophy. Alterations in CSF amine metabolite levels were related primarily to PHT intoxication, and low CSF folate and thiamine levels, but not to length of treatment or CNS atrophy. PHT intoxication increased CSF 5-hydroxyindoleacetic acid (5HIAA). Low folate levels were associated with decreased CSF 5HIAA and homovanillic acid, while low thiamine levels were associated with decreased CSF 5HIAA and 3-methyoxy-4-hydroxyphenylethylene glycol. It remains to be seen to what extent these alterations in biogenic amine metabolism, mediated by low CNS vitamin levels, also lead to deficits in cerebral function.

Negative‐ion chemical ionization spectra of oxazolidinone derivatives of amino acids prepared by their reaction with dichlorotetrafluoroacetone

AbstractOxazolidinone derivatives of glycine, phenylalanine and tyrosine were prepared by their reaction with dichlorotetrafluoroacetone. The derivatives were analyzed by gas chromatography/negative‐ion chemicalionization mass spectrometry with methane as the reagent gas. The mass spectra under these conditions were composed of a few ions resulting largely from the addition of a chlorine radical to the molecular ion and successive losses of up to two HCl moieties from the molecular ion; loss of CO2 was also observed. Comparison of the mass spectrum of glycine and [2H2]glycine indicated that the protons involved in the loss of HCl from the molecular ion were derived in the first instance from the CH2 group in the derivative and secondly from the NH group. The derivatives were applied to the analysis of the amino acid precursors of biogenic amines in nervous tissue from the locust.

Acute Effect of Protein or Carbohydrate Breakfasts on Human Cerebrospinal Fluid Monoamine Precursor and Metabolite Levels

Patients with normal pressure hydrocephalus who had three lumbar punctures during 1 week ingested either water, a protein breakfast, or a carbohydrate breakfast 2.5 h before each of the lumbar punctures. The CSF was analyzed for biogenic amine precursors and metabolites. The protein meal raised CSF tyrosine levels, a finding consistent with animal data, but did not alter those of tryptophan or any of the biogenic amine metabolites. The carbohydrate meal increased CSF 3-methoxy-4-hydroxyphenylethylene glycol, an unexplained finding. The carbohydrate meal did not affect CSF tryptophan, tyrosine, 5-hydroxyindoleacetic acid, or homovanillic acid. Our results support the idea that in humans protein or carbohydrate meals do not alter plasma amino acid levels sufficiently to cause appreciable changes in CNS tryptophan levels or 5-hydroxytryptamine synthesis.

Relationship between changes in plasma amino acids and depression in alcoholic patients.

The authors studied the relationship between changes in amino acid precursors of biogenic amines and depression in 42 alcoholic patients with a secondary depression. Tryptophan and amino acids competing with it for brain entry were measured in the plasma of depressed alcoholics, nondepressed alcoholics, and control subjects. The ratio of tryptophan to its competitors was significantly lower in depressed patients than in nondepressed patients and controls. The decreased ratio was due primarily to decreased tryptophan and increased tyrosine and phenylalanine values. A decreased tryptophan ratio is known to result in decreased brain tryptophan and may contribute to depression through a deficiency of brain serotonin.

Cerebrospinal fluid measurements suggest precursor availability and sex are involved in the control of biogenic amine metabolism in a primate.

Biogenic amine precursors and metabolites were measured in cisternal cerebrospinal fluid from 83 female and 55 male vervet monkeys. The results indicate that mean rates of 5-hydroxytryptamine, dopamine, and noradrenaline metabolism in the brain are higher in females than in males. They also suggest that under physiological circumstances tryptophan availability is involved in the control of brain 5-hydroxytryptamine synthesis while tyrosine availability is involved in control of both dopamine and noradrenaline metabolism. The similarities seen between our results on vervets and those seen with human cerebrospinal fluid suggest that the vervet is a useful primate to study.

Effect of 5-Hydroxytryptophan on Serum Cortisol Levels in Major Affective Disorders

Serum cortisol levels were significantly increased following administration of 5-hydroxytryptophan (5-HTP), 200 mg orally, to patients with affective disorders. A three- to five-week period of treatment with lithium carbonate or monoamine oxidase (MAO) inhibitor augmented the mean 5-HTP-induced increase in serum cortisol concentration in manic or depressed patients, respectively: tricyclic antidepressant (TCA) and second-generation antidepressant treatment diminished the mean serum cortisol response in patients with major depression. These results are consistent with the hypothesis that lithium carbonate may enhance serotonin (5-HT) receptor sensitivity, whereas TCA and second-generation antidepressants diminish 5-HT receptor sensitivity. The enhancement of the cortisol response to 5-HTP by MAO inhibitors may be due to decreased metabolism of 5-HT. It is important to assess the effect of thymoleptic drug treatment on various responses to biogenic amine precursors or agonists in patients rather than laboratory animals.

An Autoradiographic Study of the Taste Bud Following Injections of Labeled Biogenic Amine Precursors

An Autoradiographic Study of the Taste Bud Following Injections of Labeled Biogenic Amine Precursors Get access Masako TAKEDA, Masako TAKEDA Department of Anatomy, Higashi Nippon Gakuen University School of DentistryIshikari-Tobetsu, Hokkaido, 061-02 Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Yuko SUZUKI Yuko SUZUKI Department of Anatomy, Higashi Nippon Gakuen University School of DentistryIshikari-Tobetsu, Hokkaido, 061-02 Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Electron Microscopy, Volume 32, Issue 4, 1983, Pages 357–360, https://doi.org/10.1093/oxfordjournals.jmicro.a050425 Published: 01 January 1983 Article history Published: 01 January 1983 Received: 21 July 1983 Accepted: 18 November 1983

Biogenic amine metabolites in human lung tumor cells: Histochemical and mass-spectrographic demonstration

Three continuous cell lines isolated from small cell carcinoma of the lung (SCCL) have been examined for their ability to take up and metabolize the biogenic amine precursors, L-DOPA and 5-hydroxytryptophane (5-HTP). In two of the three lines formaldehyde-induced fluorescence (FIF) and mass-spectrographic analysis indicated specific uptake and metabolism of L-DOPA and 5-HTP.

Processing of cell debris suggestive of phagocytosis in the follicular cavities of the avian adenohypophysis

The effects of the administration of the biogenic amine precursors L-DOPA and 5-hydroxy-L-tryptophan on the ultrastructure of the nongranulated, folliculo-stellate cells of the avian adenohypophysis were investigated in an attempt to approach the function of these cells. The analysis of the ultrastructural changes induced by these compounds revealed that the folliculo-stellate cells can encircle large portions of granulated, hormonogenic cells and, subsequently, phagocytize them. After 5-hydroxy-L-tryptophan treatment, junctional complexes appeared between non-granulated and granulated cells. Moreover, a remarkable dark cytoplasm containing autophagic vacuoles was found in some folliculo-stellate cells. In view of the literature, the observations reported here argue in favour of a role in phagocytosis of cell debris and/or of surplus of secretory material, as a result of endocrine dysfunctioning. Nevertheless, the capability of transformation of hormone-producing cells into folliculo-stellate cells has to be considered.

Hypotaurine uptake in mouse brain slices.

Hypotaurine, 2-aminoethanesulfinic acid, an immediate precursor in taurine biosynthesis (3), is converted to taurine also in brain tissue (10). Hypotaurine concentration in the rat brain is 0.07 mmole/kg fresh weight, i.e. higher than that of the biogenic amine precursors, phenylalanine and tryptophan (21). Taurine transport has been studied in different nervous tissue preparations (16,19) and its penetration into brain tissue has been found to be very slow both in vivo (18) and in vitro (8) when compared to the putative amino acid transmitters. Now we have characterized the properties of hypotaurine by mouse brain slices in vitro. The uptake was found to be strikingly fast and efficient, generating exceptionally high concentration gradients and consisting of two sodium-dependent high-affinity and low-affinity transport systems.

Behavioral, electroencephalographic, and biochemical changes in porta-cava shunted rats.

Behavioral, electroencephalographic, and biochemical alterations have been studied in rats with porta-caval shunt, up to 45--50 days after the operation. No behavioral or electroencephalographic changes have been observed, while modifications of various amino acids both in plasma and brain have been found. Among all the amino acids considered of particular significance are the plasma and brain increases of tyrosine, phenylalanine, and tryptophan, since they are the precursors of biogenic amines. In fact, the increase of 5-HIAA found in regions of CNS which are richest in serotoninergic synapsis could indicate an increased turnover of 5-HT. On the other hand no significant alterations of turnover of catecholamines have been found.

Sleep and behavioral changes possibly reflecting central receptor hypersensitivity following catecholamine synthesis inhibition in man

This paper reports a marked decrease in total hours of sleep in depressed and manic patients on days 3 and 4 following discontinuation of alpha-methyl-para-tyrosine (AMPT), a specific inhibitor of the synthesis of the neurotransmitters, norepinephrine and dopamine. Discontinuation of two precursors of biogenic amines, L-dopa and L-tryptophan, produced no changes in total sleep. It is suggested that the decrease in sleep following AMPT may result from catecholamine neuronal receptor hypersensitivity induced during AMPT treatment. Animal data consistent with this hypothesis are reviewed. The importance of studying rebound phenomena following psychoactive drugs and the practical therapeutic implications of these findings are discussed.

Neurochemical changes following the administration of precursors of biogenic amines

Male Wistar rats were injected intraperitoneally with either saline, L-trytophan, D,L-5hydroxytryptophan, L-tyrosine, L-DOPA or choline and killed by the near-freezing method 15 and 45 min after injection. The brains were removed, pulverized and acetylcholine, dopamine, norepinephrine, 5-hydroxytryptamine, aspartate, glutamate, glycine and γ-aminobuttyric acid wwere extracted and concurrently measured using previously reported methods. Compared to saline injected controls, some precursors not only resulted in changes in the specific neurotransmiter systems being pertubated, but also changes in the content of other neurotransmitters.

Effects of l-dihydroxyphenylalanine (l-Dopa) and d,l,5-hydroxytryptophan (d,l,5-HTP) on reserpine-induced amnesia

In a series of experiments the effects of reserpine, l-Dopa, and d,l,5-hydroxytryptophan (d,l,5-HTP) on retention of a passive avoidance training in mice were investigated. Reserpine (2.5 mg/kg) produced amnesia when given at 120 min before but not at 30 min before or at 0, 10, 30, or 90 min following training. This time-dependent reserpine effect did not appear to be due to either an alteration in footshock sensitivity during training or to the drug producing state-dependent learning. The amnesic effect of reserpine could be blocked when both l-Dopa and d,l,5-HTP were also administered up to 10 min but not at 30 or 90 min following training. The drugs, l-Dopa or d,l,5-HTP, given alone or in higher doses, could not at any time counteract the reserpine effect. The retrograde effects of the combined administration of these biogenic amine precursors on the reserpine-induced amnesia are discussed in terms of the possible role of biogenic amines in memory formation.

Cytochemical, immunofluorescence, and ultrastructural investigations on polypeptide hormone containing cells in the intestinal mucosa of a cyclostome, Myxine glutinosa

Immunofluorescence studies showed that cells in the epithelium of the intestine of the hagfish, Myxine glutinosa, reacted with antisera to porcine glucagon, and to synthetic human gastrin, pentagastrin and caerulein. These cells were argyrophil and stained with lead-haematoxylin, resembling several mammalian polypeptide hormone-producing cells. Ultrastructurally, analogous cells were observed, which contained spherical secretion granules with a diameter of 163–178 nm. The immunoreactive cells extended from the basal lamina to the luminal surface of the gut, and may thus belong to the so-called “open type” of endocrine cells. They were separate from the insulin-containing cells of apparently “closed type” in the bile duct epithelium and from the zymogen cells of the intestine which represent the exocrine pancreas in the hagfish. No cells in the intestinal epithelium reacted with antisera to secretin or insulin. Although the immunoreactive argyrophil cells resembled mammalian gut endocrine cells in their cytochemical and ultrastructural characteristics, they did not take up and decarboxylate biogenic amine precursors. In this respect they also differed from the insulin-producing B-cells in the hagfish. Nerve fibres were observed in the submucous connective tissue but no close connections between nerve fibres and the endocrine cells were seen.