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A role for biogenic amines in developmental language disorders.

The authors discuss the current uncertainty regarding etiology, treatment, and classification of developmental language disorders (DLD). Referring to previous reports in the literature, they propose a specific subclass of DLD associated with a hypothesized dysfunction of the dopaminergic system of the basal ganglia. Mechanisms of dysfunction and treatment implications are discussed.

Basal Ganglia↗

Non-covalent and coordination interactions in Cu(II) systems with uridine, uridine 5'-monophosphate and triamine or tetramine as biogenic amine analogues in aqueous solutions.

Reactions of metallation and non-covalent interactions have been studied in ternary systems of Cu(II) ions with uridine, uridine 5'-monophosphate and diamines or triamines. It has been found that in metal-free systems the reaction centres of the nucleoside with the polyamine are the donor nitrogen atoms N(3) and protonated -NH(x) groups of the amines. In comparison to systems with adenosine or cytidine, the pH range of complex formation is shifted towards higher values. It is a consequence of significantly higher basicity of uridine and in agreement with the ion-ion, ion-dipole interaction model assumed. Formation of molecular complexes of uridine 5'-monophosphate with polyamines at a low pH is the result of activity of the phosphate group which plays the role of a negatively charged reaction site. Non-covalent interactions interfere in processes of bioligand metallation. Centres of weak interactions are simultaneously binding sites of metal ions. In protonated Cu(Urd)(PA)H(x) complexes, coordination has been found to involve the N(3) atom from the nucleoside and two donor nitrogen atoms from the polyamine (PA). In the heteroligand species Cu(Urd)(PA), despite deprotonation of all amine groups, one of these groups is located outside the inner coordination sphere. In complexes with uridine-5'-monophosphate, the phosphate group is active in metallation. Moreover, in certain coordination compounds this group is engaged in non-covalent interactions with PA molecules, despite binding Cu ions, as has been shown on the basis of equilibrium and spectral studies.

Biogenic Polyamines↗

Effect of enhanced proteolysis on formation of biogenic amines by lactobacilli during Gouda cheese ripening.

The effect of enhanced proteolysis on amine formation by amino acid decarboxylase positive Lactobacillus sp. during Gouda cheese ripening was examined. A commercial proteolytic enzyme preparation was added to pasteurized milk prior to cheese preparation. The effect of this manipulation on the formation of putrescine, histamine and tyramine was investigated in the presence and absence of amino acid decarboxylase-positive strains during a 12-week ripening period. Four batches were supplemented with a proteolytic enzyme. Batch I contained the proteolytic enzyme only, whereas batches II-IV were additionally supplemented with Lactobacillus delbrueckii LTH 1260 (batch II), Lactobacillus buchneri LTH 1388 (batch III) or Lactobacillus brevis LTH 2560 (batch IV). In batch I putrescine was detected with 4 mg/kg, in batch II, 42 mg/kg putrescine, 238 mg/kg histamine and 636 mg/kg tyramine were found. Batch III contained 13 mg/kg putrescine and 418 mg/kg histamine, whereas in batch IV, 26 mg/kg putrescine and 776 mg/kg tyramine were present. Batch V was supplemented with all three lactobacilli but did not contain the proteolytic enzyme. In this experiment, 4 mg/kg putrescine, 179 mg/kg histamine and 337 mg/kg tyramine were detected. A control cheese batch (VI) without addition of amine forming lactobacilli or a proteolytic enzyme was produced and only 4 mg/kg putrescine were detected. An increase in amine concentration during cheese ripening under conditions of enhanced proteolysis in the presence of starter and spoilage lactobacilli was evident from the experiments.

Amino Acids↗

Differential effects of L-trytophan and buspirone on biogenic amine contents and metabolism in Lurcher mice cerebellum.

The effects of serotoninergic stimulation on monoamines were studied in the heterozygous Lurcher (Lc/+) mutant mouse, a model of human cerebellar ataxia. Wild type (+/+) and Lc/+ mice were treated for 40 days with L-tryptophan or buspirone, and serotonin (5-HT), dopamine (DA), noradrenaline (NA) and their main metabolites were measured in the cerebellum. In +/+ mice, only buspirone increased concentrations of 5-HT metabolites. In the hypoplastic Lc/+ cerebellum, indoleamines were higher, and increased further after both treatments. The 5-HT turnover index was increased in +/+ mice by buspirone, while in Lc/+ mutants it increased after L-tryptophan but was decreased by buspirone, indicating that in the mutants nerve terminals synthesize and accumulate 5-HT, but may not utilize it efficiently. Catecholamine contents remained unchanged in +/+ mice, but in Lc/+ mutants with higher endogenous NA, L-tryptophan further increased NA and 3,4-dihydroxy-phenylacetic acid (DOPAC), and buspirone augmented NA, DA and DOPAC levels.

3,4-Dihydroxyphenylacetic Acid↗

Effects of p-chlorophenylalanine on striatal acetylcholinesterase activity and on biogenic amine levels in nuclei raphe and caudate-putamen during physostigmine-induced tremor in rats.

The biochemical mechanism underlying tremor is unknown. We investigated the effects of p-chlorophenylalanine (pCPA), a serotonin (5-HT) depletor, on the neurochemical processes in nuclei raphe dorsalis (NRD) and caudatus putamen (NCP) paralleling physostigmine-induced tremor in rats. Peak of physostigmine tremor correlated with increase in 5-HT in NRD and NCP, and a decrease in striatal dopamine (DA), as assayed employing high pressure liquid chromotography-electrochemistry. Administration of pCPA caused significant decrease in DA, norepinephrine (NE) and 5-HT levels in both the nuclei, without affecting striatal NE content and acetylcholinesterase activity. pCPA pretreatment significantly inhibited physostigmine-induced tremor and blocked corresponding increase in the levels of 5-HT in NRD and NCP. These results indicate involvement of central 5-HT, but not DA or NE, in the genesis of physostigmine tremor.

Acetylcholinesterase↗

Identification and quantitation of N-acetyl metabolites of biogenic amines in the thoracic nervous system of the locust, Schistocerca gregaria, by gas chromatography-negative-ion chemical ionisation mass spectrometry.

The N-acetylated metabolites of p-tyramine, p-octopamine and dopamine were identified unambiguously and quantitatively determined in a single ventral thoracic nerve cord of the locust, Schistocerca gregaria, by gas chromatography-negative-ion chemical ionisation mass spectrometry (GC-NICIMS). Deuterium-labelled analogues of each compound were added to a single ventral thoracic nerve cord in acetonitrile: the tissue was homogenised and the suspension centrifuged. The solvent was removed from the supernatant and the resultant residue was derivatised with trifluoroacetic anhydride. Under negative-ion chemical ionisation conditions, the trifluoroacetyl derivatives produced ions which were sufficiently abundant to be suitable for selected-ion monitoring. This method is highly specific and gave a limit of detection below the picogram levels. N-Acetyl-5-hydroxytryptamine was determined using a previously published GC-NICIMS technique [S.P. Markey, R.W. Colburn and J.N. Johannessen, Biomed. Mass Spectrom., 7 (1981) 301]. The concentrations of N-acetyltyramine, N-acetyloctopamine, N-acetyldopamine and N-acetyl-5-hydroxytryptamine in locust thoracic nerve cords were, respectively, 1.86 +/- 0.71, 1.13 +/- 0.34, 6.77 +/- 8.48 and 0.07 +/- 0.02 ng per tissue.

Acetic Anhydrides↗

Assay procedures for the determination of biogenic amines and their metabolites in rat hypothalamus using ion-pairing reversed-phase high-performance liquid chromatography.

Procedures are described for the simultaneous determination, by high-performance liquid chromatography of adrenaline, noradrenaline, dopamine and 5-hydroxytryptamine using laurylsulphate as pairing ion and for the separate simultaneous determination of vanillylmandelic acid, dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylethylene glycol, 5-hydroxyindoleacetic acid and homovanillic acid using tetraethylammonium as pairing ion. Sample preparation consists of protein precipitation only and octadecylsilane coated silica is used for both sets of determinations as is electrochemical detection. The chromatographic basis of each separation is discussed in the light of modern ideas of ion exchange and desolvation to enable the method to be modified chromatographically if other compounds are to be resolved or the assay method modified. The quantitative aspects of the methods are detailed and applied to amine and metabolite levels in rat hypothalamus. The values determined together with their sample variation and estimated limits of detection are quoted.

Animals↗

Presence of norepinephrine and other biogenic amines in stonefish venom.

Although fish venoms exert a cardiovascular effect, the presence of adrenergic substances was not previously demonstrated. Chromatographic analysis with electrochemical detection showed the presence of substances co-migrating with norepinephrine, dopamine and tryptophan. Serotonin, which was thought to be implicated in the intense pain following fish envenomation, was not detected. Norepinephrine was identified as a component of the stonefish Synanceia verrucosa venom by gas chromatography-mass spectrometry.

Adrenergic alpha-Agonists↗

Electrochemical monitoring of biogenic amine neurotransmission in real time.

Three techniques, constant-potential amperometry, high-speed chronoamperometry, and fast-scan cyclic voltammetry, have been used extensively to investigate the rapid events associated with neurotransmission. These techniques vary in sensitivity, chemical resolution and temporal resolution. Amperometry provides the best temporal resolution but little chemical resolution. Fast-scan cyclic voltammetry provides both good temporal and chemical resolution, while high-speed chronoamperometry offers good temporal resolution and moderate chemical resolution. The amount of chemical information which is needed for a neurochemical measurement depends upon the sample. For single cells, secondary methods, such as HPLC and capillary electrophoresis, offer extensive chemical information about the contents of a cell. With this information, chemical information is not needed during the electrochemical measurement. Therefore, amperometry is employed to obtain the greatest temporal resolution. However, when using more complex biological samples, such as brain slices or in vivo implantation, there is a greater demand for chemical resolution provided by the electrochemical measurement. To bolster results, further confirmation is sought from anatomical, physiological and pharmaceutical evidence. Within this review, the three electrochemical techniques are outlined and compared. Examples are then provided of measurements which have been made in the three predominant biological samples which have been studied: single cells, brain slices and intact animals.

Animals↗

Cloning of biogenic amine receptors from moths (Bombyx mori and Heliothis virescens).

Based on the similarity of genes which code for guanine-nucleotide binding protein- (G-protein-) coupled receptors, cDNA clones encoding new members of the receptor family have been isolated from Bombyx mori and Heliothis virescens. The deduced protein structures exhibit highest similarity to tyramine/octopamine and serotonin receptors of Drosophila. One of the receptor clones (K50Hel) was permanently expressed in the mammalian cell line LLC-PK1. In stimulation experiments its responded to octopamine leading to an inhibition of adenylate cyclase activity in a dose-dependent manner. Pharmacological studies revealed a higher affinity for mianserin than for yohimbine suggesting, that the K50Hel clone encoded a neuronal type 3 octopamine receptor. As revealed by in situ hybridization, this receptor type is expressed in the central nervous system and antennae of moth.

Amino Acid Sequence↗

The synthesis of (R)- and (S)-[N-methyl-11C]beta, beta-difluoromethamphetamine for the investigation of the binding mechanism of biogenic amines in vivo.

In an attempt to elucidate the contribution of the extent of nitrogen protonation on the in vivo binding of methamphetamine in the brain, the enantiomers of [N-methyl-11C]beta, beta-difluoroamphetamine (4) were prepared for use in positron emission tomography (PET) studies. Thus, the enantiomers of beta, beta-difluoroamphetamine were prepared from trans-beta-methylstyrene, via bromination, conversion into the azirine, fluorination and resolution as the tartrate salts. (R)- and (S)-beta, beta-difluoroamphetamine (3) were then each labelled with carbon-11 (tt/2 = 20.4 min) by N-methylation of the corresponding homochiral beta, beta-difluoroamphetamine with [11C]methyl iodide. The labelled products were each synthesised, purified and formulated in 35 min, starting from [11C]carbon dioxide in 15-16% decay-corrected radiochemical yield, with a radiochemical purity of > 99% and specific radioactivity of 50-150 GBq mumol-1 at end of synthesis.

Binding Sites↗