Serotonin and its metabolism in basal deuterostomes: insights from Strongylocentrotus purpuratus and Xenoturbella bocki.

Serotonin (5-HT), an important molecule in metazoans, is involved in a range of biological processes including neurotransmission and neuromodulation. Both its creation and release are tightly regulated, as is its removal. Multiple neurochemical pathways are responsible for the catabolism of 5-HT and are phyla specific; therefore, by elucidating these catabolic pathways we glean greater understanding of the relationships and origins of various transmitter systems. Here, 5-HT catabolic pathways were studied in Strongylocentrotus purpuratus and Xenoturbella bocki, two organisms occupying distinct positions in deuterostomes. The 5-HT-related compounds detected in these organisms were compared with those reported in other phyla. In S. purpuratus, 5-HT-related metabolites include N-acetyl serotonin, gamma-glutamyl-serotonin and 5-hydroxyindole acetic acid; the quantity and type were found to vary based on the specific tissues analyzed. In addition to these compounds, varying levels of tryptamine were also seen. Upon addition of a 5-HT precursor and a monoamine oxidase inhibitor, 5-HT itself was detected. In similar experiments using X. bocki tissues, the 5-HT-related compounds found included 5-HT sulfate, gamma-glutamyl-serotonin and 5-hydroxyindole acetic acid, as well as 5-HT and tryptamine. The sea urchin metabolizes 5-HT in a manner similar to both gastropod mollusks, as evidenced by the detection of gamma-glutamyl-serotonin, and vertebrates, as indicated by the presence of 5-hydroxyindole acetic acid and N-acetyl serotonin. In contrast, 5-HT metabolism in X. bocki appears more similar to common protostome 5-HT catabolic pathways.

Serotonin catabolism in the central and enteric nervous systems of rats upon induction of serotonin syndrome.

Serotonin, a well-known neurotransmitter in mammals, has been linked to a number of neurological and gastrointestinal disorders. One of these disorders, serotonin syndrome, is a potentially deadly condition caused by increased levels of serotonin in the extracellular space. Information on the neurochemical effects of serotonin syndrome on serotonin catabolism is lacking, particularly in relation to the enteric system of the gastrointestinal tract. Here the catabolism of serotonin is monitored in rats with pharmacologically induced serotonin syndrome, with the catabolites characterized using a specialized capillary electrophoresis system with laser-induced native fluorescence detection. Animals induced with serotonin syndrome demonstrate striking increases in the levels of serotonin and its metabolites. In the brain, levels of serotonin increased 2- to 3-fold in animals induced with serotonin syndrome. A major serotonin metabolite, 5-hydroxyindole acetic acid, increased 10- to 100-fold in experimental animals. Similar results were observed in the gastrointestinal tissues; in the small intestines, serotonin levels increased 4- to 5-fold. Concentrations of 5-hydroxyindole acetic acid increased 32- to 100-fold in the intestinal tissues of experimental animals. Serotonin sulfate showed surprisingly large increases, marking what may be the first time the compound has been reported in rat intestinal tissues.

Serotonin catabolism and the formation and fate of 5-hydroxyindole thiazolidine carboxylic acid.

Serotonin (5-HT) functions as a neurotransmitter and neuromodulator in both the central and enteric nervous systems of mammals. The dynamic degradation of 5-HT metabolites in 5-HT-containing nervous system tissues is monitored by capillary electrophoresis with wavelength-resolved laser-induced native fluorescence detection in an effort to investigate known and novel 5-HT catabolic pathways. Tissue samples from wild type mice, genetically altered mice, Long Evans rats, and cultured differentiated rat pheochromocytoma PC-12 cells, are analyzed before and after incubation with excess 5-HT. From these experiments, several new compounds are detected. One metabolite, identified as 5-hydroxyindole thiazoladine carboxylic acid (5-HITCA), has been selected for further study. In 5-HT-incubated central and enteric nervous system tissue samples and differentiated PC-12 cells, 5-HITCA forms at levels equivalent to 5-hydroxyindole acetic acid, via a condensation reaction between L-cysteine and 5-hydroxyindole acetaldehyde. In the enteric nervous system, 5-HITCA is detected without the addition of 5-HT. The levels of L-cysteine and homocysteine in rat brain mitochondria are measured between 80 and 140 microm and 1.9 and 3.4 microm, respectively, demonstrating that 5-HITCA can be formed using available, free L-cysteine in these tissues. The lack of significant accumulation of 5-HITCA in the central and enteric nervous systems, along with data showing the degradation of 5-HITCA into 5-hydroxyindole acetaldehyde, suggests that an equilibrium coupled to the enzyme, aldehyde dehydrogenase type 2, prevents the accumulation of 5-HITCA. Even so, the formation of 5-HITCA represents a catabolic pathway of 5-HT that can affect the levels of 5-HT-derived compounds in the body.

Structural and spectroscopic studies of nickel(II) complexes with a library of Bis(oxime)amine-containing ligands.

A library of tripodal amine ligands with two oxime donor arms and a variable coordinating or noncoordinating third arm has been synthesized, including two chiral ligands based on l-phenylalanine. Their Ni(II) complexes have been synthesized and characterized by X-ray crystallography, UV-vis absorption, circular dichroism, and FTIR spectroscopy, mass spectrometry, and room-temperature magnetic susceptibility. At least one crystal structure is reported for all but one Ni/ligand combination. All show a six-coordinate pseudo-octahedral coordination geometry around the nickel center, with the bis(oxime)amine unit coordinating in a facial mode. Three distinct structure types are observed: (1) for tetradentate ligands, six-coordinate monomers are formed, with anions and/or solvent filling out the coordination sphere; (2) for tridentate ligands, six-coordinate monomers are formed with Ni(II)(NO(3))(2), with one monodentate and one bidentate nitrate filling the remaining coordination positions; (3) for tridentate ligands, six-coordinate, bis(mu-Cl) dimers are formed with Ni(II)Cl(2), with one terminal and two bridging chlorides filling the coordination sphere. The UV-vis absorption spectra of the complexes show that the value of 10 Dq varies according to the nature of the third arm of the ligand. The trend based on the third arm follows the order alkyl/aryl < amide < carboxylate < alcohol < pyridyl < oxime.