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Neurobehavioral effects of permethrin are associated with alterations in regional levels of biogenic amine metabolites and amino acid neurotransmitters.

Oral administration of 120 or 240 mg/kg permethrin produced dose- and time-related tremor in rats with the peak effect occurring 5 hrs after dosing. Subsequent experiments done 5 hrs postdosing found that 45 to 180 mg/kg permethrin produced dose-related increases in rectal temperature and enhanced responsiveness to an acoustic stimulus. Tremor was detected at 90 and 180 mg/kg. Neurochemical analyses of regional biogenic amines and their metabolites and amino acids 5 hrs after 90 or 180 mg/kg indicated that 5-HIAA levels were increased in the hypothalamus (HYP), brain stem (BS), hippocampus (HPC), and striatum (STR); 5-HT was not affected. MHPG was increased in the HYP and BS, while NE was decreased at the high dose only. DOPAC and HVA were increased in the STR after 90 and 180 mg/kg, while DA was not affected. Aspartate levels were increased in the BS and STR; glutamate was increased in the BS. Taurine, glutamine, glycine, and GABA were not affected. A time-course analysis of neurochemical changes 2, 5, 12, and 24 hrs postdosing indicated that 5 hrs was the time of peak effect for permethrin. Permethrin-induced tremor and hyperthermia were significantly correlated with dose- and time-related changes in MHPG, 5-HIAA, and ASP.

Amino Acids↗

Effects of chronic diazepam and medazepam treatment on the level of biogenic monoamines in different rat brain areas.

Studies were made of the effect of 19-day administration of diazepam (1 mg.kg-1, i.p.) and medazepam (5 mg.kg-1, i.p.) on the level of biogenic monoamines in different rat brain areas: cerebral cortex, striatum, hippocampus, and hypothalamus. The noradrenaline (NA), dopamine (DA) and serotonin (5-HT) levels were determined. After chronic treatment with diazepam no alterations in the NA content in the cortex, striatum and hypothalamus were found. Medazepam increased the NA level in the cortex, striatum, and hippocampus without changing it in the hypothalamus. Repeated administration of diazepam or medazepam led to an increase in the DA level in the striatum. Both benzodiazepines provoked a significant increase in the hippocampal 5-HT level, which could be attributed to the antianxiety effect of these drugs.

Animals↗

Biogenic amines as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells (review).

The role of extracellular amines such as noradrenaline and serotonin and their interaction with cyclic nucleotides and intracellular polyamines in the regulation of intestinal epithelial cell proliferation is reviewed with particular reference to the differences between normal and neoplastic cells. In respect to the normal epithelium of the small intestine there is a strong case to support the notion that cell proliferation is controlled by, amongst other things, sympathetic nerves. In colonic carcinomas, antagonists for certain serotonin receptors, for histamine H2 receptors and for dopamine D2 receptors inhibit both cell division and tumour growth. Because of the reproducible variations between tumour lines in the response to these antagonists, this inhibition appears to be due to a direct effect on the tumour cells rather than an indirect effect via the tumour host or stroma. This conclusion is supported by the cytocidal effects of toxic congeners of serotonin on the tumour cells. The most salient difference between the amine responses of normal and neoplastic cells relates to the issue of amine uptake. Proliferation of crypt cells is promoted by amine uptake inhibitors, presumably because they block amine re-uptake by the amine secreting cells--sympathetic neurones and enteroendocrine cells. However, tumour cell proliferation is strongly inhibited by amine uptake inhibitors, suggesting that neoplastic cells can, and need to take up the amine before being stimulated by it. Recent revelations in the field of oncogenes also support an important association between amines, cyclic nucleotides and cell division. The ras oncogenes code for a protein that is a member of a family of molecules which relay information from extracellular regulators, such as biogenic amines, to the intracellular regulators, including cyclic nucleotides. Evidence is presented suggesting that enteroendocrine cells, enterocytes, carcinoid tumour cells and adenocarcinoma cells all have the same embryonic origin and that cells exhibiting an admixture of endocrine and proliferative properties exist in colonic tumours, but not in the normal intestinal epithelium. Thus, it appears that in the normal intestine a clear structural and functional distinction exists between the regulating cells (i.e. the sympathetic neurones and enteroendocrine cells) and the regulated cells (i.e. the undifferentiated crypt cells): cells that have acquired a regulating role are no longer able to divide and cells which are able to divide do not take up or store amines.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Adrenocortical hormone rhythm in blood and metabolism of the hypothalamic biogenic amines in rats].

Restricted daily feeding (RF), in which free access to food and water is restricted to a fixed time of the day, has been demonstrated to elevate the plasma corticosterone level in rats prior to meal (prefeeding corticosterone peak). But the central mechanism for the hormone peak is unknown. In this study, the metabolism of the hypothalamic biogenic amines was investigated to know whether or not it was associated with the prefeeding corticosterone peak under RF. Male rats were subjected to RF (meal time from 10:00 to 12:00 h) under the light-dark cycle (lights from 06:00 to 18:00 h). Norepinephrine metabolism was estimated from the rate of decrease in norepinephrine content after the administration of a synthesis blocker, alpha-methyl-p-tyrosine (alpha-MPT). Dopamine and serotonin metabolisms were estimated from the accumulation rate of precursor amine after the inhibition of aromatic L-amino acid decarboxylase by m hydroxybenzylhydrazine (NSD 1015). Rats were sacrificed by decapitation and four hypothalamic nuclei (SCN, PVN, VMH, LH) were punched out according to Palkovits method. Amine contents in each nucleus were measured by HPLC. Results obtained are as follows; 1) Catecholamine was significantly involved in the formation of prefeeding corticosterone peak under RF in rats. 2) Norepinephrine metabolism was different in each hypothalamic nucleus. Especially, that in PVN seems to be parallel with the plasma corticosterone level under RF. This result suggests that norepinephrine in PVN stimulates corticotropin releasing hormone (CRH). 3) Dopamine metabolism in the four hypothalamic nuclei showed similar changes; prefeeding rise (except for VMH), high activity during feeding, decrease after food deprivation, and persistence of high activity during fast. 4) Serotonin metabolism in the four hypothalamic nuclei showed similar changes; prefeeding rise (except for VMH), decrease during feeding, and persistence of high activity during fast.

Animals↗

Hyperthyroidism induces supersensitivity to biogenic amines in rat vascular tissue via a pre- and a postjunctional mechanism.

The effect of hyperthyroidism was investigated on the sensitivity of rat aortic and mesenteric arteries to the contractile effects of biogenic amines, K+ and Ca++. Supersensitivity to norepinephrine, methoxamine and clonidine was observed in the mesenteric artery. Methoxamine and clonidine are immune to disposition by neuronal and extraneuronal uptake, and supersensitivity to norepinephrine persisted in the presence of hydrocortisone and desmethylimipramine, suggesting that the supersensitivity was postjunctional in origin. In addition, reserpine pretreatment induced supersensitivity to norepinephrine in control mesenteric arteries, but in hyperthyroid mesenteric arteries no further increase in sensitivity was observed after reserpine pretreatment supporting a postjunctional mechanism. In the aorta, a small increase in sensitivity was observed to norepinephrine, no supersensitivity was detected to methoxamine and supersensitivity to norepinephrine was not apparent in the presence of hydrocortisone, suggesting a prejunctional mechanism. The existence of a small prejunctional component in the mesenteric artery also was indicated, as incubation with hydrocortisone attenuated the degree of supersensitivity after thyroid hormone pretreatment. In the mesenteric artery, postjunctional supersensitivity also was observed to 5-hydroxytryptamine. However, no increase in sensitivity was observed to KCl or CaCl2 suggesting that the postjunctional supersensitivity was not due to an increase in the sensitivity of the contractile apparatus, and was specific for receptor-mediated effects of agonists.

Animals↗

Occurrence of biogenic amines in the pancreatic islets of sand rats (Psammomys obesus).

The islets of Langerhans of sand rats (Psammomys obesus) have been investigated ultrahistochemically in order to demonstrate biogenic amines. It could be found that amine-containing vesicles with a diameter of 600-700 nm from the type of catecholamine-granules exist in A-cells as well as in B-cells. It can be stated that the sand rat belongs to the species containing amines in A- and B-cells. The importance of the amines for the regulation of the hormone secretion of the islets of Langerhans is discussed and the connections to diabetes mellitus are referred too.

Animals↗

[Effect of some fragments of peptide hormones on the content of biogenic monoamines from mouse brain].

The effect of some tripeptides, which are fragments of peptide hormones, and their analogs on the content of biogenic monoamines (BM) from albino mice brain was studied. It was found that thyroliberin, melanostatin and the C-terminal tripeptide of gonadoliberin activate the dophaminergic (DA-ergic) system in the forebrain of mice treated with reserpine or haloperidol, whereas the C-terminal tripeptide of gastrin acts as a synergic blocker of the DA receptors. The N-terminal tripeptides (with and without the amido group) do not affect the content of BM. No effect of the tripeptides was observed in intact animals. It is assumed that the agonistic or antagonistic effect of the tripeptides on BM is due to certain structural peculiarities of the tripeptides, e.g. the presence of the C-terminal amido group and their endogenous nature.

Animals↗

Effect of combined exposure to cadmium and ethanol on regional brain biogenic amine levels in the rat.

The effect of ethanol ingestion on regional brain biogenic amine levels in cadmium exposed animals was examined. The rats were given either ethanol (1 g/kg, first week, 5 g/kg, second week and 10 g/kg for rest of the weeks) or cadmium (40 ppm in drinking water) or a combination of both for 8 weeks. Simultaneous exposure to cadmium and ethanol produced a greater elevation of norepinephrine in hypothalamus and mid brain when compared with rats receiving only cadmium. A significant elevation of 5-hydroxy-tryptamine in medulla oblongata was also noticed in cadmium and ethanol treated rats compared to cadmium alone treatment animals. The present results suggest industrial workers consuming alcohol may be more susceptible to cadmium neurotoxicity.

Animals↗

A sensitive, fast, durable, highly selective method for the determination of amino acids and biogenic amines in the cerebrospinal fluid and other body fluids and tissues.

A sensitive, fast, durable HPLC method with high resolution for the determination of amino acids and some biogenic amines is described. It allows the simultaneous determination of more than 40 substances in the cerebrospinal fluid or other body fluids or tissues. The method allows to measure both, the free and the conjugated amino acids. It detects 5 X 10(-13) g of most amino acids and measures the relevant substances in their physiological concentrations with less than 0.1 ml cerebrospinal fluid. The precision is 1-2%.

Amino Acids↗

[External respiratory function, blood oxygenation and the biogenic amine content in different hemodynamic variants of hypertension].

Pulmonary ventilation and hemodynamics, ventilation/perfusion ratios, arterial blood oxygen and plasma biogenic amines were examined in 126 essentially hypertensive patients with different hemodynamic types. Changes in pulmonary ventilation and hemodynamics result in increased venous admixture in patients with eukinetic hemodynamics, but the arterial blood oxygen level only diminishes in the hypokinetic type. Increased venous admixture is due to a regional decrease in the ventilation/perfusion ratio which is largely dependent on pulmonary hemodynamic disorders. A direct correlation is demonstrated between arterial blood oxygen concentration and daily noradrenaline excretion in eu- and hypokinetic hemodynamic types. Arterial hypoxemia may be responsible for depressed sympathetic activity in patients with these circulation types.

Adolescent↗

Effects of fluorostigmine, toxogonin and atropine on monoamine oxidase activity and the level of biogenic amines in mouse brain.

Effects of fluorostigmine, toxogonin and atropine on monoamine oxidase activity and the level of biogenic amines in mouse brain. Acta physiol. pol., 1979, 30 (4): 437--444. Fluorostigmine (DFP) given i.p. to mice in doses of 1.2 and 2.45 mg/kg reduced MAO activity in the brain. Given in doses of 0.6 and 1.2 mg/kg it reduced the level of noradrenaline and dopamine as well as 5-hydroxytryptamine in the brain. DFP in such doses had no effect on the brain level of 5-hydroxyindoloacetic acid. Toxogonin (5 mg/kg i.p.) or atropine (5 mg/kg i.p.) given together with DFP reduced or abolished completely the inhibitory effect of DFP.

Animals↗

Ontogenetic development of the monoamine oxidase activity and of the metabolism of biogenic monoamines in rat brain.

The article examines the ontogenetic development of the monoamine oxidase activity and of the metabolism of the dopamine, noradrenaline and serotonin in the brain of newborn, 10-day-, 20-day- and 2-month-old rats. Monoamine oxidase activity is determined using three substrates: tyramine, serotonin and beta-phenylethylamine. Monoamine oxidase A (substrate serotonin) and the total monoamine oxidase activity (substrate tyramine) are found to manifest identical development, their activity increasing quickly after birth, to reach constant values after the 10th day. The general course of the development during the first ten postnatal days shows that the post partum increase in the total monoamine oxidase activity in rat brain is predominantly due to monoamine oxidase A. Monoamine oxidase B (substrate beta-phenylethylamine) develops after the 10th postnatal day. Evidently monoamine oxidase A plays a decisive role for controlling the level of the biogenic monoamines in the young organism during the first days of the ontogenesis. Investigation of the changes in the content of dopamine, noradrenaline and serotonin in the age groups of the experimental animals chosen reveals a rapid increase in the dopamine and noradrenaline levels even during the first ten days of the ontogenesis. The increased total monoamine oxidase activity and the increased dopamine content correspond to its increased turnover rate during ontogenesis. The turnover rate of noradrenaline remains unchanged between the 10th and 20th postnatal days. The increasing serotonin level between the 20th and 60th post partum days corresponds to its increased turnover rate.

Aging↗

[Presence of biogenic amines in the Langerhans' islets of the sand rat (Psammomys obesus) (author's transl)].

The islets of Langerhans of sand rats (Psammomys obesus) have been investigated ultrahistochemical in order to demonstrate biogenic amines. It could be found that amine containing vesicles with a diameter of 600 to 700 nm from the type of catecholamine granules exist in A-cells as well as in B-cells. Further, 2 very rare cell types not containing specific hormone granules could be found. These cells contain particles, in one case similar to catecholamine granules and in the other case representing serotonine-like granules according to their electron optical properties. It can be stated that the sand-rat belongs to the species containing amines in A- and B-cells. Moreover they contain 2 amines simultaneously. The importance of the amines for the regulation of the hormone secretion of the islets of Langerhans is discussed and the connections to the diabetes mellitus are refered to.

Animals↗

[Disorders of oxidative deamination of biogenic amines in the myocardium in experimental atherosclerosis].

Statistically significant inhibition of oxidative deamination of several biogenic amines was found in mitochondrial fraction of heart muscle from rabbits and rats with experimental atherosclerosis and hypercholesterolemia, caused by various methods. Sensitivity of oxidative deamination of tryptamine to inhibitory effect of clorgyline (selective inhibitor of mitochondrial monoamine oxidases) was unaltered in rats with experimental hypercholesterolemia. The rate of oxidative deamination of beta-phenyl ethylamine, tryptamine, benzylamine as well as histamine and putrescine was inhibited after treatment of the mitochondrial fragments from healthy rabbit and rat heart muscles with preparations of oxidized linoleic and linolenic acids, concentration of which was increased in tissues under conditions of atherosclerosis.

Animals↗

[Biogenic amine content and the pathomorphological shifts in different organs and tissues in a period of the hematogennic spread and fixation of botulin toxin].

In experiments on cats it was shown that 30 minutes after intravenous injection of botulinum toxin, type C, there was a fall in the catecholamine and histamine contents with a simultaneous increase of serotonin in various structures of the brain and spinal cord and in a number of inner organs as well. The metabolic changes in the biogenic amines were combined with certain pathomorphologic changes seen in the form of acute swelling, chromatolysis, destruction of some neurons of the spinal cord and brain, distrophic changes in inner organs, and an increased permeability of the blood-tissue barriers. Marked biochemical and pathomorphologic changes in the spinal cord and brain where the minimum concentration of toxin becomes manifest during its spreading allow a conclusion that botulinum neurotoxin shows its pathogenic action through a disturbed metabolism of biologically active substances.

Animals↗

Reaction of blood pressure and mesenteric blood flow to an infusion of biogenic amines in rats: influence of irradiation and alpha blockers.

The reaction of systemic blood pressure and mesenteric blood flow to an infusion of different biogenic amines was determined in controls and in lethally (8 Gy) X-irradiated rats. The influence of the alpha blocker phenoxybenzamine on these reactions was also investigated. Changes in blood pressure and flow response similar to, but less marked than, those seen earlier after a supralethal (20 Gy) exposure were detected 3 and 7 days after irradiation. These observations as well as the consequences of alpha blockade suggest that the reactivity of alpha receptors in blood vessels is reduced after irradiation, and that the function of the heart is impaired.

Acetylcholine↗

Action of certain pharmacological associations on the level of cerebral biogenic amines and some metabolites in the curative treatment of hemorrhagic shock in rats.

Different associations of pharmacological agents were tested in the curative treatment of hemorrhagic shock, using as criteria the variations of cerebral biogenic amines (NE, DA, 5-HT) and some of their metabolites (DOPAC, HVA, 5-HIAA). These values were compared to those observed in controls two hours after the reinjection of effused blood. Prior work had led to the use of each component of these therapeutic associations and the reasons having suggested their association are summarized. The results show that the most active association for antagonizing the changes of the above amines and metabolites is that of tyrosine, 15% glucose, insulin and vitamin C. The results are discussed.

Adenosine↗

Influence of the antidepressant binodaline on biogenic amine uptake and brain levels in the rat.

The influence of 1-(omega-dimethylaminoethylmethyl)-amino-3-phenylindole hydrochloride (binodaline, Sgd-Scha 1059) on the uptake of noradrenaline (norepinephrine, NA), 5-hydroxytryptamine (5-HT) and dopamine (DA) into pre-synaptic nerve endings has been studied using purified synaptosomal preparations from various regions of rat brain. Binodaline was found to be an effective inhibitor of biogenic amine uptake the IC50 values being 5.0 X 10(-6) mol/l (NA), 2.3 X 10(-7) mol/l (5-HT) and 1.5 X 10(-6) mol/l (DA). The desmethyl analogue of binodaline (Sgd 20578) also inhibited transmitter uptake into cerebral nerve endings, being more potent than the parent compound in inhibiting NA uptake (8.5 X 10 mol/l), of a similar potency with respect to 5-HT (3.2 X 10(-7) mol/l) and slightly less potent against DA (8.3 X 10(-6) mol/l). Neither binodaline nor the desmethyl derivative was found to influence cerebral levels of NA, 5-HT and DA following acute dosing in rats. Brain concentrations of the related metabolites 5-hydroxyindolacetic acid, dihydroxyphenylacetic acid and homovanillinic acid were also unchanged. It is concluded that binodaline owes its antidepressant activity at least in part to its ability to inhibit monoamine uptake into pre-synaptic cerebral nerve endings.

Animals↗