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At least 253 records · Page 14Linked to original sources

Analysis of the biogenic amines in the central nervous system of the tobacco hornworm by high-performance liquid chromatography with 16-sensor electrochemical detection.

A method was developed to analyze biogenic amines in extracts of the central nervous system of the tobacco hornworm, Manduca sexta by high-performance liquid chromatography with 16-sensor electrochemical detection (n-EC-HPLC). The amines, precursors, and metabolites were separated in two dimensions. The first dimension involves separation based upon retention time by reversed-phase HPLC, while the second dimension involves separation based upon the characteristic oxidation potentials achieved by n-EC. Biogenic amine identification was based upon maximum oxidation potential and peak height ratios in addition to retention time. The improved resolving power of this method allows for a simplified sample preparation procedure and simultaneous determination of a wide range of compounds, including phenylethylamine, catecholamines, indoleamines, and some of their precursors and metabolites.

Animals↗

From synapse to vesicle: the reuptake and storage of biogenic amine neurotransmitters.

Biogenic amine transport systems in the presynaptic plasma membrane and the synaptic vesicle provide a mechanism for rapidly terminating the action of released transmitters and for recycling neurotransmitters. Alterations in the activity of these transporters, either by endogenous regulatory mechanisms or by drugs, affect the regulation of synaptic transmitter levels. For drugs such as antidepressants and stimulants that interact with these transport systems, the therapeutic and behavioral consequences are profound. Now that the cDNAs encoding the transporters have been isolated, we can expect rapid progress in understanding how the individual proteins work at the molecular level to couple ion gradients to the reuptake and storage of biogenic amine neurotransmitters.

Amino Acid Sequence↗

Rearing experience and biogenic amine activity in infant rhesus monkeys.

In this report we present evidence that early social experience influences aspects of the function of brain biogenic amine systems, most notably the noradrenergic system. Biogenic amine activity was studied in mother- vs. peer-reared monkey infants over the first 6 months of life and in response to two housing transitions. Norepinephrine (NE), 3-methoxy-4-hydroxyphenylglycol (MHPG), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) levels in cerebrospinal fluid (CSF) were measured. Peer-reared monkeys showed significantly higher CSF levels of norepinephrine and MHPG than mother-reared animals over early development, but showed an attentuated NE response to separation and group formation compared to mother-reared animals. Peer-reared monkeys showed a greater developmental decline in 5-HIAA levels than mother-reared monkeys. There were no rearing effects for DOPAC or HVA over early development; however, peer-reared monkeys showed significantly lower HVA and DOPAC concentrations at 6-8 months of age. The results add to evidence for the influence of primate mothers on the psychobiological development of central nervous system neurotransmitter systems in their infants, and suggest that the noradrenergic system is among the more sensitive of these to early experience.

Aging↗

Quantitative localization of biogenic amines in the spinal cord.

Recently developed highly sensitive radiometric assays for biogenic amines have been combined with microdissection techniques to localize and quantify these amines in different structures, and at various levels of rabbit and rat spinal cords. Assays were performed for serotonin, norepinephrine, dopamine and epinephrine. It was generally found that the highest concentrations of those biogenic amines were found in the lateral and ventral horns, slightly lesser concentrations were found around the central canal, and still lower concentrations were found in the dorsal horns. Relatively low amine concentrations were found in the white matter. These biochemical measurements correlate well with localizations indicated by histofluorescence methods but provide precise quantification. Comparisons with previously available, less sensitive biochemical measurements are discussed.

Animals↗

The effect of biogenic amine modifiers on morphine analgesia and its antagonism by naloxone.

The stimulation of dopaminergic receptors, inhibition of serotonin synthesis or blockade of muscarinic receptors by various modifiers led to inhibition of morphine analgesia in mice. Blockade of dopaminergic receptors or the increase in serotonergic or cholinergic activity resulted in the enhancement of morphine analgesia. Serotonergic and cholinergic systems are proposed as positive and the dopaminergic system as negative modulators of morphine analgesia. The modulation of naloxone antagonism was much more complicated than that of morphine analgesia and often the effect of biogenic amine modifiers on antagonism differed from that on analgesia. The fact than biogenic amine modifiers do not affect morphine analgesia and naloxone antagonism by a similar pattern suggests that interaction of narcotics and narcotic antagonists with analgesic receptors may not be exactly the same.

Analgesia↗

Studies on the capacity of mazindol and dita to act as uptake inhibitors or releasing agents for 3H-biogenic amines in rat brain tissue slices.

The effects of the anorexic and stimulant agents mazindol and dita on 3H-biogenic amine uptake and release were determined. Mazindol and dita were very potent inhibitors of 3H-norepinephrine uptake into rat brain occipital cortex slices with ED50 values (point of 50% inhibition of uptake) of 1.5 X 10(-9) M and 3.2 X 10(-9) M, respectively. Mazindol (ED50 of 2.8 X 10(-7) M) and dita (ED50 value of 8.5 X 10(-7) M) were also potent inhibitors of 3H-dopamine uptake into rat neostriatal slices and of 3H-serotonin uptake into whole brain slices (ED50 values of 5.5 X 10(-7) M and 5.1 X 10(-7) M for mazindol and dita respectively). Both compounds proved however to be extremely weak releasing agents for the 3H-biogenic amines in the respective brain areas. The effects of mazindol and dita on uptake may help to explain some of their pharmacological properties.

Acetophenones↗

Blockade by antidepressants and related compounds of biogenic amine uptake into rat brain synaptosomes: most antidepressants selectively block norepinephrine uptake.

Inhibitor constants (Ki's) for blocking uptake of [3H]norepinephrine, [3H]serotonin, and [3H]dopamine into synaptosomal preparations of rat brain were determined for 25 antidepressants and putative antidepressants, some neuroleptics, stimulants, antihistamines and other monoamines. With Ki's we could directly and definitively compare the relative potencies of a drug at the three processes. Eighteen or 72% of the antidepressants (including tertiary amine tricyclics) were more potent at blocking uptake of norepinephrine than at blocking uptake of serotonin. Considering all three biogenic amines, 17 antidepressants were selective for blocking [3H]norepinephrine uptake, one (bupropion) was selective although weak for blocking [3H]dopamine uptake, and the remainder were selective for blocking [3H]serotonin uptake. The neuroleptics chlorpromazine and promazine were relatively potent at blocking uptake of [3H]norepinephrine and some tricyclic antidepressants (notably, trimipramine and butriptyline) were very weak at blocking any biogenic amine uptake.

Animals↗

Centrally mediated hemodynamic effects of cocaine in rabbits: the role of local anesthetic actions and biogenic amine re-uptake blockage.

This study sought to identify the central nervous system-mediated cardiovascular effects of cocaine and to determine if these effects result from local anesthetic action or biogenic amine re-uptake blockade. New Zealand rabbits received multiple i.c.v. doses of cocaine, pseudococaine, lidocaine or desipramine while recording blood pressure and heart rate. Moderate dose cocaine produced a decrease in heart rate and mean arterial pressure while the highest dose produced increases in heart rate and blood pressure. Lidocaine and pseudococaine produced dose-dependent increases in blood pressure while desipramine produced decreases in heart rate and mean arterial pressure. In this model, the central nervous system-mediated cardiovascular effects of cocaine are dose-dependent; low doses produced cardiovascular depression while higher doses produced cardiovascular stimulation. The data also suggest that cocaine's local anesthetic effects are responsible for its central nervous system-mediated cardiovascular stimulation, while biogenic amine re-uptake blockade causes cardiovascular depression.

Adrenergic Uptake Inhibitors↗

A simple method for concentration of biogenic amines and their metabolites from biological samples for analysis by HPLC-EC.

This report describes a new rapid, convenient and inexpensive method of concentrating biogenic amines and their metabolites from biological samples for analysis by HPLC-EC. Recovery of standard monoamines and metabolites from artificial cerebrospinal fluid (CSF) solution following lyophilization in the presence of glutathione (1.2 mg/ml, final concentration) and EGTA (1.8 mg/ml, final concentration) was greater than 89%; the coefficient of variation was 0.6-3.7%, depending on the specific amine or metabolite concentrated. Lyophilization as a one step procedure is suitable for concentrating biogenic amines and metabolites from biological fluids such as CSF that contain low concentrations of protein and other interfering substances. When concentrating compounds from plasma, which contains large quantities of protein and other electrochemically active materials, it is necessary to add an extraction step, such as alumina extraction. By substituting 0.05 M HCl for the conventional eluent, 0.1 M HClO4, we were able to increase recoveries of catecholamines from plasma by approximately 20%. Recovery of endogenous catecholamines from plasma following the combined alumina extraction - lyophilization procedure was 81 +/- 1%.

Animals↗

Simultaneous measurement of tetrahydrobiopterin (THBP) and biogenic amines by liquid chromatography with electrochemical detection.

This report describes a rapid and sensitive method for measuring tetrahydrobiopterin (THBP) and biogenic amines simultaneously by liquid chromatography with electrochemical detection (LC-ECD). The coefficient of variation for THBP was 4.87% and the minimum detectable amount of THBP was approximately 20 pg. These results indicate that this simple reverse-phase ion-pair chromatography system can be used for the simultaneous analysis of endogenous THBP and biogenic amines without long sample preparation time.

Animals↗

Altered cerebrospinal fluid amino acid pattern in the anorexia of aging: relationship with biogenic amine metabolism.

To study the possible role of several amino acids on feeding in the anorexia of aging, we have measured plasma and cerebrospinal fluid (CSF) concentrations of 22 amino acids in 14 elderly persons with idiopathic anorexia and 10 healthy subjects with normal weight in a similar age range. Plasma and CSF amino acid concentrations and CSF homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) levels were all measured by HPLC methods. Elderly anorectic subjects had significantly lower levels of glutamic acid but increased concentrations of glutamine in both plasma and CSF compared to controls. Likewise, a significant increase of histidine, threonine, alanine, arginine, valine, methionine, isoleucine, leucine, phenylalanine, tryptophan, ornithine and lysine was found in CSF, but not in plasma, from patients with anorexia. Besides, the CSF histidine/LNAA (large neutral amino acids) and tryptophan/LNAA ratios were elevated in anorectic patients as compared with controls of similar age. In addition, we found higher CSF concentrations of HVA and 5-HIAA, as well as a positive correlation between CSF LNAA and either HVA (r = 0.74, p = 0.002) or 5-HIAA (r = 0.61, p = 0.020) concentrations in elderly anorectics. CSF tryptophan correlated positively with 5-HIAA levels (r = 0.59, p = 0.026) and CSF tyrosine with HVA levels (r = 0.77, p = 0.002). Our results suggest that changes in the CSF concentration of amino acids could contribute to an increased biogenic amine metabolism in the central nervous system of elderly anorectic subjects, possibly increasing the synaptic liberation of biogenic amines involved in the appetite regulation.

Aged↗

Hypophysectomy does not alter the effects of somatostatin or growth hormone on canine splanchnic biogenic amine release.

We have demonstrated previously that growth hormone (GH) and somatostatin (somatotropin release inhibitory factor, SRIF) exert comparable effects on the release of splanchnic biogenic amines. The purpose of the present investigation was to study further the response of the two hormones and see whether the similarity persists in dogs completely deprived of endogenous GH. Experiments were conducted in seven hypophysectomized dogs fitted with an indwelling portal catheter. Two to 4 weeks after surgery the responsiveness of their catecholaminergic neurons was tested by an injection of human beta-endorphin (20 micrograms/kg); it caused a rise in portal catecholamine levels equivalent to that seen in intact dogs. Then the effect of a spike concentration of SRIF or GH on hepatic portal and peripheral levels of free serotonin and catecholamines was studied, all by radioenzymatic methods. The intravenous injection of ovine GH (100 micrograms/kg) or equimolar amounts of SRIF (7.5 micrograms/kg) produced in the hepatic portal circulation a transient but statistically significant rise of serotonin and a concomitant reduction in the concentration of dopamine, norepinephrine, and epinephrine. No changes were found in the peripheral circulation. The response patterns to SRIF or GH were virtually identical, which is in keeping with our other data, suggesting that the effect of GH on splanchnic biogenic amine secretion is SRIF-dependent and mediated by SRIF-containing neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Voluntary drinking of ethanol by the rat: biogenic amines and possible underlying mechanism.

The present study evaluates the possible relationship between certain biogenic amine metabolites-produced changes in voluntary drinking of ethyl alcohol (ET) solution by the rat and their in vivo effects on the enzymes primarily involved in the hepatic metabolism of ET, i.e., liver alcohol-(L-ADH) and aldehyde dehydrogenase (L-ALDH). In experiments on voluntary intake of ET solution by the rat, compounds selected were injected, 0.5 mM/kg, IP. Administration of vanillylmandelic acid (VMA) and 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) markedly reduced ET drinking. Similar significant effects were seen after administration of the neutral metabolites of the biogenic amines tested, after injection of metanephrine or 3-methoxy-4-hydroxyphenylpyruvic acid. Threodihydroxyphenylserine but not L-dopa reduced ET intake by the rat. Treatment with peripheral decarboxylase inhibitors, i.e., carbidopa, 50 mg/kg, IP, significantly reduced ET drinking as contrasted with nonsignificant decline in ET consumption following benserazide, 500 mg/kg, IP. In the biochemical study, short-term administration of the compounds selected produced varied effects on L-ADH and L-ADH. It is suggested that alteration of hepatic ADH by the compounds tested might account for the observation reduced ET drinking thereby, indicating the contribution of peripheral sources rather than central factors in mediating the behavioral effects studied.

Alcohol Drinking↗

Evaluation of toluene exposure via drinking water on levels of regional brain biogenic monoamines and their metabolites in CD-1 mice.

Toluene, a potentially neurotoxic substance, is found in trace amounts in groundwater. Adult male CD-1 mice were continuously fed drinking water ad libitum containing 0, 17, 80, and 405 mg/liter toluene. After a 28-day treatment, animals were tested for endogenous levels of the biogenic monoamines norepinephrine (NE), dopamine (DA), and serotonin (5-HT) and their respective metabolites. 3-methoxy-4-hydroxymandelic acid (VMA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), in six discrete brain regions. The maximum toluene-induced increases of biogenic amines and their metabolites generally occurred at a toluene concentration of 80 mg/liter. In the hypothalamus, a major NE-containing compartment, the concentrations of NE significantly increased by 51, 63, and 34% in groups dosed with 17, 80, and 405 mg/liter, respectively. Significant increases of NE were also observed in the medulla oblongata and midbrain. Concomitantly, concentrations of VMA increased in various brain regions. Concentrations of DA were significantly higher in the corpus striatum and hypothalamus. Alterations in levels of DA metabolites, DOPAC and HVA, were marginal. Toluene significantly increased concentrations of 5-HT in all dissected brain regions, except cerebellum, and increased the 5-HIAA levels in the hypothalamus, corpus striatum, and cerebral cortex.

Animals↗

Effects of benzo[a]pyrene on steady-state levels of biogenic amines and metabolizing enzymes in mouse brain regions.

Benzo[a]pyrene (BaP) is a product of incomplete fossil fuel combustion, a well-known pollutant, and a carcinogenic agent. In the present study male CD-1 mice received ip injections of 0, 5, 25, and 100 mg/kg body weight BaP twice a week for 3 weeks. Endogenous levels of brain biogenic amines and their selected metabolites, norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), vanillylmandelic acid, dihydroxyphenylacetic acid (DOPAC), homovanillic acid, and 5-hydroxyindoleacetic acid (5-HIAA) were measured using high performance liquid chromatography and electrochemical detection. The brain regions studied were cortex, striatum, hypothalamus, midbrain, medulla oblongata, and cerebellum. BaP treatment increased the steady-state levels of NE, DA, and 5-HT in the hypothalamus and striatum. Increased levels of DA and 5-HT and their major metabolites DOPAC and 5-HIAA were noticed in the same region, an indication of increased metabolism of these amines. The increase in the 5-HT level in the cortex was not dose-related. Levels of NE and DA were significantly higher in the medulla oblongata. There was a concurrent increase in activities of tyrosine hydroxylase and tryptophan hydroxylase in several brain regions. The effect of BaP on Dopa-decarboxylase was not consistent. Monoamine oxidase was occasionally inhibited. Results indicate that exposure to BaP altered the steady-state levels of biogenic amines in various brain regions and these changes were consistent with the activities of metabolizing enzymes.

Animals↗

A multidimensional approach to analysis of cerebrospinal fluid biogenic amines in schizophrenia: II. Correlations with psychopathology.

As part of a multidimensional study of cerebrospinal fluid biogenic amine metabolites in schizophrenia, the relationship between neurochemical measures and psychopathology assessed using the Psychiatric Symptom Assessment Scale (PSAS) was analyzed. In a group of 20 unmedicated patients, 3,4-dihydroxyphenylacetic acid (DOPAC) was a predictor of symptom severity in a stepwise multiple regression model. Values of 3-hydroxykynurenine and metanephrine in the unmedicated state predicted clinical response in a stepwise multiple regression model, as measured by improvement in PSAS mean item score following 6 weeks on a standard dose of neuroleptic. In a subgroup of 14 patients in whom both off- and on-medication concentrations of cerebrospinal fluid biogenic amines and metabolites were measured, change in 3-hydroxykynurenine predicted clinical outcome in a multiple regression model. These findings point toward the need to examine the role of the kynurenine pathway of tryptophan metabolism in the pathophysiology of schizophrenia.

Adult↗

Biogenic monoamines in the freshwater snail, Biomphalaria glabrata: influence of infection by the human blood fluke, Schistosoma mansoni.

The biogenic monoamines, serotonin (5-HT), dopamine (DA) and L-dopa were measured using high performance liquid chromatography with electrochemical detection (HPLC-ED) in the extracts of the central nervous system (CNS) and plasma of uninfected freshwater snails, Biomphalaria glabrata, and in snails at 7, 14, 21 and 28 days postexposure (PE) to the miracidia of the human blood fluke, Schistosoma mansoni. Relative to age-matched uninfected snails, a general depression of biogenic amine levels was observed in the plasma (cell-free haemolymph) and the CNS of infected snails, especially during the latter phase of the prepatency period. Significant decreases were first observed in the CNS of infected snails beginning at Day 14 PE for DA and 5-HT and Day 21 PE for L-dopa. Parasite-exposed snails also exhibited an early and persistent suppression of plasma 5-HT concentrations, starting at 7 days PE and continuing throughout the infection test period. In order to determine the effect of 5-HT on reproduction and, thereby, establish a possible relationship between the observed parasite-induced reduction in 5-HT levels and parasitic castration, the effect of exogenous 5-HT on individual infected and uninfected B. glabrata was investigated. Repeated treatment with 10 microM 5-HT promoted both ovulation and oviposition in B. glabrata. Snails treated with 5-HT consistently layed more eggs than did sham-treated controls. Infected snails that were treated with 5-HT exhibited similar egg-laying rates as those of both serotonin-treated and untreated, uninfected snail groups, thus reversing the castrating effects of larval infection. These findings suggest that 5-HT acts as a stimulant for egg production in B. glabrata, and that parasitic castration may be due, at least in part, to larval-induced suppression of 5-HT in the snail's CNS and plasma during the course of infection with S. mansoni.

Animals↗

Effect of calcium on the histochemical distribution and intensity of biogenic amine-containing neurons in the mouse brain.

The effect of calcium on the biogenic amine level and distribution in the mouse brain was investigated by a histochemical method using a microscopic photometer (Pl, Nikon). Histochemical fluorescence intensities in the corpus striatum and cortex cerebri regions were significantly increased by the intraventricular administration of CaCl2. This result suggests that calcium increases biogenic amine levels. These results are consistent with our previous pharmacological and biochemical findings.

Animals↗