Tryptophan (Trp), serotonin (5-HT), monoamino oxidase (MAO) and 5-hydroxyindole acetic acid (5-HIAA) in brain and subesophagic ganglions of earthworms. Effects of Parathion

Summary Tryptophan, 5-HT, MAO and 5-HIAA were determined in the first 5 segments of earthworms (Oligochaetae) where the brain and subesophagic ganglions are located. Tranylcypromine (IMAO) decreased MAO activity increasing 5-HT and decreasing 5-HIAA. Motility and survival of worms were disturbed. InAllolobophora species (young worms), parathion fumigation decreased acetylcholinesterase (AChE) activity and increased Trp, 5-HT and 5-HIAA. Motility was diminished after 24 h: it worsened after 72, but returned to normal levels 40/50 days later.Publication of the National Institute of Agrarian Technology (INTA), Argentina.Acknowledgments. We are most grateful to Prof. Zlatko Tomsic (from the Lillo Institute, Tucumán) and to Leticia Alvarado (from INTA) and to Prof. Mirta P. de Matosian for earthworm classification.     

Advantages ofn-heptanol in the extraction of 5-hydroxytryptamine (5-HT)

Zusammenfassung Mitn-Heptanol als Extraktionsmittel können kleine Mengen von 5-Hydroxytryptamin (5-HT) aus biologischem Material, das 5-Hydroxytryptaphan (5-HTP) in grossen Mengen enthält, extrahiert werden.     

Lane-Emden equation (LEE) of index 5 and Padé approximations

Summary The approximate analytical solution of Lane-Emden equation of index 5 has been found in the form of the rational function. The problem of the accuracy of this solution is briefly discussed.     

The effect of thyroid gland on 5-Hydroxy-tryptamine (5-HT) level of brain stem and blood in rabbits

Zusammenfassung An Kaninchen wurde die Wirkung von Schilddrüsenfütterung und Thyreoidektomie auf das 5-HT-Niveau im Hirnstamm und Blut untersucht. In hyperthyreotischem Zustand ist der 5-HT-Spiegel im Blut und im Hirnstamm erhöht, bei Athyreose ist er verringert. Der Schilddrüseneffekt wird in der Veränderung des Tryptophan- Stoffwechsels über das zentrale Nerven-system gesehen.     

The diterpenoid alkaloid noroxoaconitine is a Mapkap kinase 5 (MK5/PRAK) inhibitor

The mitogen-activated protein kinase-activated protein kinase MK5 is ubiquitously expressed in vertebrates and is implicated in cell proliferation, cytoskeletal remodeling, and anxiety behavior. This makes MK5 an attractive drug target. We tested several diterpenoid alkaloids for their ability to suppress MK5 kinase activity. We identified noroxoaconitine as an ATP competitor that inhibited the catalytic activity of MK5 in vitro (IC₅₀ = 37.5 μM; K _i = 0.675 μM) and prevented PKA-induced nuclear export of MK5, a process that depends on kinase active MK5. MK5 is closely related to MK2 and MK3, and noroxoaconitine inhibited MK3- and MK5- but not MK2-mediated phosphorylation of the common substrate Hsp27. Molecular docking of noroxoaconitine into the ATP binding sites indicated that noroxoaconitine binds more strongly to MK5 than to MK3. Noroxoaconitine and derivatives may help in elucidating the precise biological functions of MK5 and may prove to have therapeutic values.     

d-5-Chloro-2-(α-hydroxybenzyl)benzimidazole and 1-Alkyl-5-chloro-2-(α-hydroxybenzyl)benzimidazoles as inhibitors of poliovirus multiplication

Zusammenfassung Died-isomere Verbindung ist verantwortlich für die Poliovirus-hemmende Aktivität vondl-5-Chlor-2-(-oxy-benzyl)-benzimidazol.dl-1-Propyl-5-chlor-unddl-1-Butyl-5-chlor-Derivate sind ausserordentlich wirksam zur Verhinderung der Vermehrung der Typen 1, 2 und 3 des Poliovirus; andere 1-Alkyl-5-chlor-Derivate sind ebenfalls aktiv. Die 1-Alkyl-Grundverbindungen sind jedoch wirksamer als deren gleichartige 1-Alkyl-5-chlor-Derivate.

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The research is supported by the National Fund for Research into Poliomyelitis and other Crippling Diseases.     

Prolongation of hypnosis by 5-hydroxytryptamine (Serotonin)

Zusammenfassung Die Angabe, dass 5-Oxytryptamin (Serotonin) die Chloralhydrat- oder Barbitursäure-Hypnose bei Mäusen verlängern kann, wurde bestätigt. Da aber Stoffe wie Adrenalin und Histamin den gleichen Effekt zeigten, erscheint es möglich, dass die hypnoseverlängernde Eigenschaft des 5-Oxytryptamin auf einen relativ unspezifischen, vaskulären Effekt zurückzuführen ist.     

Synthesis of bradykinin potentiating pentapeptide (BPP5a)

Summary This synthesis is especially suitable for production of highly-purified bradykinin-potentiating pentapeptide (BPP_5a) because of the high yields of the coupling and deprotection reactions, accompanied by minimal side reactions, and the need for only one simple final purification step.The authors wish to thankJ. Pallak for carrying out the aminoacid analyses and bio-assays.     

5-(3-Pyridyl)tetrazole,a potent and long-acting lipolysis inhibitor

Zusammenfassung Es wird gezeigt, dass 5-(3-Pyridyl)-Tetrazol und Nikotinsäure die Menge der unveresterten Fettsäuren (UFS) bei fastenden Hunden erniedrigen. Die Tetrazolanalogverbindung der Nikotinsäure hat eine längere Wirkungsdauer als Nikotinsäure, obwohl ihre antilipolytische Wirksamkeit in vitro viel geringer als die der Nikotinsäure ist. Die verlängerte Wirkung von 5-(3-Pyridyl)-Tetrazol wird als Folge seiner Stoffwechselbeständigkeit aufgefasst.     

Sleep and monoamines: differential radioautography of central neurons after systematic injection of tritiated 5-hydroxytryptophane (5 HTP 3H) or of dihydroxyphenylalanine (DOPA 3H)]

In normal cats 90 min. after the intravenous injection of 5 mg/kg of 5 HTP and 3H 5 HTP or DOPA and 3H DOPA a few reactive nerve cell bodies were identified by radioautography. On the contrary, 48 hrs. after p-chlorophenylalanin or subtotal lesion of raphe nuclei, these tracers showed numerous reactive neurons inside or outside the central monoaminergic systems.     

Antagonismus zwischen Heparin und 5-Hydroxytryptamin (Serotonin)in vitro

Summary In the isolated rat colon and uterus, heparin caused inhibition or elimination of contractions occurring after the administration of 5-hydroxytryptamine. In contrast to this, neither Tyrode's solution, nor glycogen, nor dextran produced any change in the response of these organs to 5-hydroxytryptamine.     

5-Methoxy- and 5-hydroxy-indolealkylamines in the skin ofBufo alvarius

Riassunto Gli estratti di pelle diBufo alvarius, rospo delle regioni desertiche del Nord America, contengono, oltre alle consuete 5-idrossiindolalchilamine (5-HT, N-metil-5-HT, bufotenina) enormi quantitativi di derivati 5-metossiindolici, rappresentati soprattutto daO-metilbufotenina. Questa può giungere a costituire fino il 16% del peso delle ghiandole cutanee secche. Si insiste sulla probabile presenza di 5-idrossiindolo-O-metiltransferasi nella pelle diBufo alvarius.

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Supported by a grant from the Consiglio Nazionale delle Ricerche, Roma.     

MLL5 (KMT2E): structure,function, and clinical relevance

The mixed lineage leukemia (MLL) family of genes, also known as the lysine N-methyltransferase 2 (KMT2) family, are homologous to the evolutionarily conserved trithorax group that plays critical roles in the regulation of homeotic gene (HOX) expression and embryonic development. MLL5, assigned as KMT2E on the basis of its SET domain homology, was initially categorized under MLL (KMT2) family together with other six SET methyltransferase domain proteins (KMT2A–2D and 2F–2G). However, emerging evidence suggests that MLL5 is distinct from the other MLL (KMT2) family members, and the protein it encodes appears to lack intrinsic histone methyltransferase (HMT) activity towards histone substrates. MLL5 has been reported to play key roles in diverse biological processes, including cell cycle progression, genomic stability maintenance, adult hematopoiesis, and spermatogenesis. Recent studies of MLL5 variants and isoforms and putative MLL5 homologs in other species have enriched our understanding of the role of MLL5 in gene expression regulation, although the mechanism of action and physiological function of MLL5 remains poorly understood. In this review, we summarize recent research characterizing the structural features and biological roles of MLL5, and we highlight the potential implications of MLL5 dysfunction in human disease.