Biomedical subjects

S Senoh

Publications and source records attributed to S Senoh.

10 recordsLinked to original sources

PubMed1986

Drug-induced changes in histamine and tele-methylhistamine levels in mouse peripheral tissues.

To clarify the histamine (HA) dynamics in peripheral tissues, effects of drugs on the tissue HA and tele-methylhistamine (t-MH) levels were studied in mice. alpha-Fluoromethylhistidine (50 mg/kg, i.p.) significantly decreased the HA level in the stomach, but not in the liver, heart, ileum, submandibular gland and skin of mice. This compound had no significant effect on the t-MH level in any tissue examined. In non-fasted and 24-hr fasted animals, the t-MH level in the liver, heart and ileum was significantly increased by treatment with aminoguanidine (10 mg/kg, i.p.) plus pargyline (65 mg/kg, i.p.). However, in mice fasted for 48 hr, this treatment was ineffective in increasing the t-MH level in the heart and ileum, suggesting that the t-MH level in some peripheral tissues is under the influence of the food intake. Even if HA is synthetized and then metabolized in the peripheral tissues, the size of the HA pool with a rapid turnover in each tissue except for the gastric tissue seems to be very small.

Animals↗

PubMed1980

Cleavage of pyrogallol by non-heme iron-containing dioxygenases.

Both intradiol and proximal extradiol dioxygenases are thought to produce the same product, alpha-hydroxymuconic acid, when pyrogallol (3-hydroxycatechol) is used as a substrate. However, when these enzymes were reacted with pyrogallol, they gave different products. A proximal extradiol dioxygenase, metapyrocatechase (catechol:oxygen 2,3-d-oxidoreductase (decyclizing), EC 1.13.11.2), gave a product having an absorption maximum at 290 nm, which was gradually converted to a more stable compound having an absorption maximum at 239 nm. On the other hand, an intradiol dioxygenase, protocatechuate 3,4-dioxygenase (protocatechuate:oxygen 3,4-oxidoreductase (decyclizing), EC 1.13.11.3), gave a product having an absorption maximum at 300 nm. Based on the spectral data and direct comparison with authentic samples, the primary products obtained by the action of the former and the latter enzymes were identified as alpha-hydroxymuconic acid and 2-pyrone-6-carboxylic acid, respectively. While another intradiol dioxygenase, pyrocatechase (catechol:oxygen 1,2-oxidoreductase (decyclizing), EC 1.13.11.1), gave a mixture of nearly equimolar amounts of these two compounds. Isotope labeling experiments indicated that 1 atom of oxygen was incorporated in 2-pyrone-6-carboxylic acid from the atmosphere. Based on these findings, the reaction mechanism for the formation of 2-pyrone-6-carboxylic acid is discussed. This may be the first experimental evidence indicating the presence of a seven-membered lactone intermediate during the oxygenative cleavage of catechols, proposed by Hamilton (Hamilton, G.A. (1974) in Molecular Mechanisms of Oxygen Activation (Hayaishi, O., ed) pp. 405-451, Academic Press, New York).

Catechol 2,3-Dioxygenase↗

PubMed1979

Formation of 5-hydroxykynurenine and 5-hydroxykynurenamine from 5-hydroxytryptophan in rabbit small intestine.

In order to clarify the role of indoleamine 2,3-dioxygenase [indole:oxygen 2,3-oxidoreductase (decyclizing), EC 1.13.11.17] in the metabolism of serotonin, DL-5-hydroxy[methylene-(14)C]tryptophan, a precursor of serotonin, was incubated with slices of rabbit ileum. Resulting metabolites were separated by DEAE-cellulose column and polyamide column chromatography and identified by various chromatographic techniques and enzymatic analysis. Metabolites obtained in significant amounts were serotonin, 5-hydroxyindoleacetic acid, 5-hydroxytryptophol, 5-hydroxykynurenine, 5-hydroxykynurenamine, and 4,6-dihydroxyquinoline, representing 13.2, 15.8, 7.0, 21.9, 1.3, and 2.6% of the total metabolites, respectively. The first three compounds were previously reported to be major metabolites produced from 5-hydroxytryptophan by the action of aromatic L-amino acid decarboxylase and monoamine oxidase, whereas the last three are formed by the cleavage of the indole ring by the action of indoleamine 2,3-dioxygenase. In the presence of pargyline, a monoamine oxidase inhibitor, the major metabolites obtained were serotonin, 5-hydroxykynurenine, and 5-hydroxykynurenamine, representing 29.6, 26.6, and 5.4% of the total metabolites, respectively. In the presence of RO4-4602, an aromatic amino acid decarboxylase inhibitor, 5-hydroxykynurenine was the sole major product. These results strongly suggest that the newly discovered metabolic pathway involving the cleavage of the indole ring of 5-hydroxytryptophan operates in vivo to a significant extent and that indoleamine 2,3-dioxygenase plays an important role in the regulation of serotonin levels in the small intestine of the rabbit.

5-Hydroxytryptophan↗

PubMed1978

Effects of indoleamines and their newly identified metabolites on prolactin release in rats.

Plasma immunoreactive PRL responses to indoleamines and their metabolites were studied in urethane-anesthetized rats. All drugs were injected into the lateral ventricle and blood samples were serially collected from a jugular vein. Serotonin and melatonin caused a significant increase in plasma PRL with peak values at 10-20 min after the injection. Significant increase in plasma PRL were also observed after the administration of 5-hydroxykynurenamine (5-HK), a newly identified serotonin metabolite. The potency of 5-HK was less than that of serotonin but much greater than that of melatonin. In contrast, plasma PRL did not change significantly in response to N-acetyl-5-methoxykynurenamine, another newly identified metabolite of melatonin, or a vehicle solution. Simultaneous administration of melatonin significantly blunted the plasma PRL response to serotonin, whereas the rise in plasma PRL induced by 5-HK was not blunted by melatonin. These results suggest that indoleamines as well as their metabolites play a role in regulating PRL secretion in rats.

5-Hydroxytryptophan↗

PubMed1976

Antagonism of 5-hydroxykynurenamine against serotonin action on platelet aggregation.

Serotonin induced an aggregation of human platelets, whereas 5-hydroxykynurenamine, produced from serotonin by the action of indoleamine 2,3-dioxygenase, did not cause any significant degree of platelet aggregation. 5-Hydroxykynurenamine specifically inhibited both a serotonin-induced aggregation of platelets and the potentiation of the ADP-induced platelet aggregation by serotonin. It did not, however, alter the profiles of the platelet aggregation induced by ADP, collagen, or adrenaline. The degree of inhibition was proportional to the time of preincubation of platelets with 5-hydroxykynurenamine, and to the concentration of 5-hydroxykynurenamine used. Available evidence indicated that 5-hydroxykynurenamine completed with serotonin for the same receptor sites. Studies with analogues of 5-hydroxykynurenamine indicated that the substitutions of 0-amino-benzyl moiety with hydroxy or methoxy groups were somewhat tolerated, whereas the masking of alkylamine moiety with N-acetylation completely lost the inhibitory activity.

Adenosine Diphosphate↗

PubMed1975