5-Hydroxytryptamine biological activity

Important products derived from amino acids include heme, purines, pyrimidines, hormones, neurotransmitters, and biologically active peptides. In addition, many proteins contain amino acids that have been modified for a specific function such as binding calcium or as intermediates that serve to stabilize proteins—generally structural proteins—by subsequent covalent cross-hnk-ing. The amino acid residues in those proteins serve as precursors for these modified residues. Small peptides or peptide-like molecules not synthesized on ribosomes fulfill specific functions in cells. Histamine plays a central role in many allergic reactions. Neurotransmitters derived from amino acids include y-aminobutyrate, 5-hydroxytryptamine (serotonin), dopamine, norepinephrine, and epinephrine. Many drugs used to treat neurologic and psychiatric conditions affect the metabolism of these neurotransmitters. 

Several pharmacologically active substances are present in superfusates of the cerebral cortex, including acetylcholine, 5-hydroxytryptamine, substance P and the prostaglandins. Members of this latter family of hydroxy-unsaturated fatty acids are released from a great variety of tissues on nerve and hormone stimulation (Ramwell and Shaw 1970), and have been shown to possess a wide range of biological activity (Horton, 1969). 

The simplest unsubstituted indole and its methyl derivative, scatol, were found in some Lepiota and Tricholoma species. The probable biogenetic precursor of all indole metabolites is the amino acid tryptophan, widely distributed in fungi, or its derivative tryptamine, found in some species of Coprinus, Inocybe, Panaeolus, Sacrodon, and Boletus (7). Investigation of a strong biological activity characteristic of an animal hormone function revealed the presence 5-hydroxytryptamine (serotonin), which was found in large amounts in some Panaeolus and Amanita species. 

In mammals, conversion of L-tryptophan to 5-hydroxy-tryptophan (7) is the first step in the formation of the biologically active amine serotonin or 5-hydroxytryptamine (Fig. 13.16) (Udenfriend et al., 1956). 5-Hydroxytryptophan has been isolated from the legume Mucuna pruriens as well as from cotton and bananas (Rosenthal, 1982). 

Recent in vitro experiments have demonstrated the possibility that biologically active amines may be incorporated into the body protein. Using isotopes, it was shown that phenylethylamine, putrescine, histamine, cadaverine, colamine, methylamine, noradrenaline, and 5-hydroxytryptamine... 

The third chapter A Frontier in Indole Chemistry 1-Hydroxyindoles, 1-Hydroxytryptamines, and 1-Hydroxy tryptophans by Masanori Somei presents a very comprehensive review on chemistry of 1 -hydroxy-indoles, -tryptamines, and -tryptophans as a frontier in indole chemistry. In fact, these new members of indole derivatives were not much known about 30 years ago in the long histry of indole alkaloids and related chemistry. Nowadays, these new families of indole compounds have been demonstrated to play their important role in life and nature by the pioneering works of Somei and his coworkers. The interesting biological and pharmaceutical activities have been found in these derivatives. 

Several amines are known to have specific biological functions. Some obvious examples are histamine and serotonin (5-hydroxytryptamine), which are produced by decarboxylation of the corresponding amino acids. The secondary amine, epinephrine, is formed in an incompletely elucidated pathway from phenylalanine. In addition to these compounds with potent pharmacological activity, other amines seem to play vital... 

One of the major problems associated with the isolation of small relatively unstable polypeptides from biological tissue is that the peptides may break down or undergo other chemical transformation during the extraction procedures. Recently, a new approach to the study of the chemical nature of CRF has been developed [293] which overcomes this problem. Jones, Hillhouse and Burden [293] demonstrated that 5-hydroxytryptamine selectively stimulates the release of CRF, but not vasopressin, from hypothalamic tissue in vitro and attempts are now being made to isolate and identify the CRF in the incubation medium. Preliminary separation by chromatography on Sephadex G-25 demonstrated two peaks of CRF activity, fraction A and B, with molecular weights of around 2500 and 1300 respectively. Both fractions evoked dose-related increases in pituitary ACTH release either when injected into basal hypothalamic-lesioned rats or when incubated with adenohypophysial tissue in vitro but Fraction A was the more potent in this respect. Neither fraction markedly influenced the release of... 

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