N-Acétylation enzymatique de la tryptamine par des homogénats de cerveaux deLocusta migratoria avant et après intoxication par le chlordimeform ou le lindane

Summary Brain homogenates ofLocusta migratoria are found to possess enzyme capable of catalyzing the N-acetylation of tryptamine. A main product of the enzymatic reaction is isolated and identified as N-acetyltryptamine by chromatography analyse. Both insecticides, chlordimeform and lindane, inhibit enzyme activity. A direct correlation between the degree of intoxication and acetylation of tryptamine is described.     

Inhibition of tryptophan uptake in Aspergillus fumigatus by tryptamine

Summary The tryptophan uptake was inhibited considerably in tryptamine grown cells. This inhibition was due to feed-back inhibition and not to repression.The authors are greatful to Prof. V. V. Modi for his interest in this work. The award of research fellowship by M. S. University of Baroda to A. R. G. is greatfully acknowledged.     

Effects of tranylcypromine and pargyline on brain tryptamine

Summary Tranylcypromine produces behavioral excitation while pargyline produces depression. Tranylcypromine increased brain tryptophan which led to an accumulation of tryptamine. The levels of tryptamine after tranylcypromine were found to be 3 times those found after pargyline.This work was supported in part by U. S. Public Health Service Grants NS-12759 and AA-2696, State of Illinois Department of Mental Health, the Psychiatric Services Branch, Province of Saskatchewan, and the Medical Research Council of Canada, who have provided continuing financial support.Acknowledgments. We thank Dr B. A. Davis for synthesizing the deuterated internal standards, Dr D. A. Durden for supervising the mass spectrometric analyses, and Mr H. Miyashita, Mr N. F. Binder and Miss E. E. Johnson for skilled technical assistance.     

The unique substrate specificity of human AOC2, a semicarbazide-sensitive amine oxidase

Semicarbazide-sensitive amine oxidases (SSAOs) catalyze oxidative deamination of primary amines, but the true physiological function of these enzymes is still poorly understood. Here, we have studied the functional and structural characteristics of a human cell-surface SSAO, AOC2, which is homologous to the better characterized family member, AOC3. The preferred in vitro substrates of AOC2 were found to be 2-phenylethylamine, tryptamine and p-tyramine instead of methylamine and benzylamine, the favored substrates of AOC3. Molecular modeling suggested structural differences between AOC2 and AOC3, which provide AOC2 with the capability to use the larger monoamines as substrates. Even though AOC2 mRNA was expressed in many tissues, the only tissues with detectable AOC2-like enzyme activity were found in the eye. Characterization of AOC2 will help in evaluating the contribution of this enzyme to the pathological processes attributed to the SSAO activity and in designing specific inhibitors for the individual members of the SSAO family. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Comparative study of the sensitivity of acetylcholinesterases and cholinesterases from animal and bacterial sources to inhibition by serotonin and its derivatives.

Serotonin was found to inhibit human erythrocyte and electric-eel acetylcholinesterase activities. The serotonin amino group, free of negative charges in its vicinity and its hydroxyl group, were important for the inhibition. Serotonin precursors and several related compounds had little or no effect. Human plasma cholinesterase was also inhibited by serotonin and tryptamine. In contrast to these animal enzymes, the cholinesterase of Pseudomonas aeruginosa was refractory to serotonin and its derivatives under the same experimental conditions.     

Comparative study of the sensitivity of acetylcholinesterases and cholinesterases from animal and bacterial sources to inhibition by serotonin and its derivatives

Summary Serotonin was found to inhibit human erythrocyte and electric-eel acetylcholinesterase activities. The serotonin amino group, free of negative charges in its vicinity and its hydroxyl group, were important for the inhibition. Serotonin precursors and several related compounds had little or no effect. Human plasma cholinesterase was also inhibited by serotonin and tryptamine. In contrast to these animal enzymes, the cholinesterase ofPseudomonas aeruginosa was refractory to serotonin and its derivatives under the same experimental conditions.     

The role of sialic acid in 5-HT binding to synaptic membranes.

The high affinity binding of [14C]5-HT to nerve ending membranes isolated from rat brain is not affected by neuraminidase treatment. The specificity of ligand receptor interaction was demonstrated by displacement studies with tryptamine derivatives, noradrenaline, and acetylcholine.     

Chemical excitability of axons: excitatory and inhibititory effects of putative neurotransmitters and modulators on frog sciatic nerves.

The microiontophoretic administration of putative neuromodulators (acetylcholine, norepinephrine, dopamine, 2-phenylethylamine, tryptamine, histamine) triggered firing or inhibited on-going activity in isolated frog sciatic nerves.     

A novel quantitative application of thin layer chromatography: Assay of tryptamine

Résumé Les auteurs décrivent une technique microchromatographique d'adsorption sur couches minces de Kieselguhr, avec l'acétone comme éluant, dans laquelle le déplacement de la part de tryptamine est proportionnel à la quantité de ce corps dans le domaine compris entre 0,025 et 2,0µg. On peut ainsi déterminer 0,10µg de tryptamine par ml de plasma. Il est fort probable que cette méthode simple et quantitative pourra également être adaptée à de nombreux autres composés.     

Effects of tranylcypromine on the concentrations of some trace amines in the diencephalon and hippocampus of the rat

Summary Concentrations of 4 trace amines in diencephalon and hippocampus of the rat were measured by integrated-ioncurrent mass spectrometry after administration of the antidepressant drug, tranylcypromine. Much larger increases were observed for 2-phenylethylamine and tryptamine than for m- and p-tyramine.Financial support has been provided by the Medical Research Council of Canada, the Psychiatric Services Branch, Province of Saskatchewan, the Alberta Mental health Research Fund, and the Special Services and Research Committee, University of Alberta Hospital.Acknowledgments. The authors wish to thank Dr B.A. Davis for synthesizing the deuterated internal standards and Dr D.A. Durden for supervising the mass spectral analyses. Expert technical assistance was provided by Mr R.C. Mag-Atas and Ms D.G. Calverley. The advice and encouragement of Professors W. G. Dewhurst and A. A. Boulton are gratefully acknowledged.     

The role of sialic acid in 5-HT binding to synaptic membranes

Summary The high affinity binding of [¹⁴C]5-HT to nerve ending membranes isolated from rat brain is not affected by neuraminidase treatment. The specificity of ligand receptor interaction was demonstrated by displacement studies with tryptamine derivatives, noradrenaline, and acetylcholine.The expert technical assistance of Miss Christiane von Winterfeld is appreciated. This work was supported by a grant of the Deutsche Forschungsgemeinschaft.     

Extraadrenal adrenaline formation by two separate enzymes

Summary Adrenaline (A) is synthesized in the adrenal medullae by the enzyme phenylethanolamine-N-methyltransferase (PNMT). After surgical removal of the adrenal medullae tissue A levels ranged from 22% of control in the heart to 125% of control in the liver. Use of a novel assay to measure tissue A formation revealed that many tissues can synthesize A using PNMT and another enzyme that N-methylates both noradrenaline and dopamine. These enzymes are non-neuronal, inducible and synthesize a major fraction of tissue and urine A.     

Extraadrenal adrenaline formation by two separate enzymes

Adrenaline (A) is synthesized in the adrenal medullae by the enzyme phenylethanolamine-N-methyltransferase (PNMT). After surgical removal of the adrenal medullae tissue A levels ranged from 22% of control in the heart to 125% of control in the liver. Use of a novel assay to measure tissue A formation revealed that many tissues can synthesize A using PNMT and another enzyme that N-methylates both noradrenaline and dopamine. These enzymes are non-neuronal, inducible and synthesize a major fraction of tissue and urine A.     

Biogenic amine acetylation: No detectable circadian rhythm in whole brain homogenates of the insectOstrinia nubilalis

Summary With the biogenic amines tryptamine, dopamine, and octopamine as substrates, N-acetyltransferase activity shows no detectable circadian rhythm in homogenates of whole brains of the European corn borerOstrinia nubilalis (Lepidoptera: Pyralidae). The circadian clock of this insect may be fundamentally different from the N-acetyltransferase pacemaker in the pineal gland of vertebrates.     

Studies on the hydrolysis of bradykinin by angiotensin-converting enzyme (kininase II)

Summary Arg-Pro-Pro-Gly-Phe, the N-terminal pentapeptide of bradykinin, is not an inhibitor of angiotensin-converting enzyme and is not hydrolyzed by the enzyme. Arg-Pro-Pro, the N-terminal tripeptide is a relatively potent (IC₅₀=2.3×10⁶ M) inhibitor but its higher homolog, Gly-Arg-Met-Lys-Arg-Pro-Pro is not an inhibitor of angiotensin-converting enzyme.This work was supported in part by grants from the US Public Health Service (HL 18415, HL 15691, HL 19764) and the John A. Hartford Foundation, Inc., and by the Medical Research Service of the Veterans Administration.     

Formation of carthamin by a partially purified enzyme from safflower seedlings

Summary An enzyme responsible for synthesizing carthamin from precarthamin was partially purified and the catalytic properties were investigated.Acknowledgments. The authors wish to thank Prof. A. Komamine, University of Tokyo, for reading this paper. We are indebted to Prof. A. Saito, Tokai University, for performing emission spectrochemical analysis of the enzyme protein used in this study.     

Mapping of restriction enzyme cuts by a new two-dimensional procedure

A new procedure has been worked out to establish restriction maps. The method is fast, does not in general require labeled DNA and has been applied to map the linear palindromic rDNA of Physarum with the restriction enzyme Bst EII.     

Beeinflussung der Gerinnungswirkung von Heparin durch Serotonin und Tryptamin

Summary Investigations in the cofactor-fibrinogen system have shown that serotonin and tryptamine, although only in relatively high doses, reduce the antithrombin time prolonged by the action of heparin. Histamine has no such effect on the action of heparin, nor have tyramine and isoamylamine.

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Für wertvolle Ratschläge im Verlaufe der Untersuchungen sind wir den Herren Dr.R. Marbet, Dr.André Studer und PD Dr.A. Winterstein, Wissenschaftliche Laboratorien der F. Hoffmann-La Roche & Co. AG. in Basel zu Dank verpflichtet.     

The presence of β-phenylethylamine,p-tyramine,m-tyramine and tryptamine in ganglia and foot muscle of the garden snail (Helix aspersa)

Summary The concentrations of -phenylethylamine,p-tyramine,m-tyramine,m-octopamine and tryptamine in the ganglia or foot muscle ofHelix aspersa range from <0.6 to 11 ng/g.p-Octopamine levels are higher in ganglia (327 ng/g) than in foot muscle (4.1 ng/g). Dopamine and 5-hydroxytryptamine range from 840 to 2710 ng/g while their acid metabolites, 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylacetic acid and 5-hydroxyindoleacetic acid range from <20 to 130 ng/g.Acknowledgments. We thank Dr A.A. Boulton for helpful discus sion, Dr D.A. Durden for supervising the mass spectrometric analyses, Dr B.A. Davis for the synthesis of the deuterated standards, G.H. Wheatley, E.P. Zarycki and M. Mizuno for expert technical assistance, and Saskatchewan Health and the MRC of Canada for providing financial support.     

Inactivation of human glutamate dehydrogenase by aluminum

Aluminum inactivated glutamate dehydrogenase (GDH) by a pseudo-first-order reaction at micromolar concentrations. A double-reciprocal plot gave a straight line with a k_inact of 2.7 min^-1 and indicated the presence of a binding step prior to inactivation. The inactivation was strictly pH dependent and a marked increase in sensitivity to aluminum was observed as the pH decreased. At a pH higher than 8.5, no inactivation was observed. The completely inactivated GDH contained 2 mol of aluminum per mole of enzyme subunit monomer. When preincubated with enzyme, several chelators such as citrate, NaF, N-(2-hydroxyethyl) ethylenediaminetriacetic acid or ethylenediaminetriacetic acid efficiently protected the enzyme against the aluminum inactivation. In a related experiment, only citrate and NaF released the aluminum from the completely inactivated aluminum-enzyme complex and fully recovered the enzyme activity. Ferritin, NADP⁺, or nerve growth factor did not show any effects on the recovery of the aluminum-inactivated GDH activity. The dissociation constant for the aluminum-enzyme complex was calculated to be 5.3 M. Although aluminum has been known to form a complex with nucleotides, no such effects were observed in the inactivation of GDH by aluminum as determined using GDHs mutated at the ADP-binding site, NAD⁺-binding site or GTP-binding site. Circular dichroism studies showed that the binding of aluminum to the enzyme induced a decrease in helices and sheets and an increase in random coil. Therefore, inactivation of GDH by aluminum is suggested to be due to the conformational change induced by aluminum binding. These results suggest a possibility that aluminum-induced alterations in enzymes of the glutamate system may be one of the causes of aluminum-induced neurotoxicity.Received 25 July 2003; received after revision 27 August 2003; accepted 15 September 2003