In Vitro Interaction of 5-Hydroxytrptamine with Cytosolic Molybdenum Hydroxylases as a Potential Inhibitor for Initial Rates Activities

Abstract

Problem statement: The role of 5-HT has been investigated in many behavioral activities. Thus, studies using raphe lesion showed that 5-HT is involved in sleep, general activity levels, habituation, aggression, pain sensitivity and morphine analgesia, avoidance behavior, self-stimulation and water consumption. Approach: The metabolic interaction between serotonin (5- hydroxytrptamine) and indole-3-aldehyde and xanthine via aldehyde oxidase (EC 1.2.3.1) and xanthine oxidase (EC 1.1.3.22), respectively, were studied in liver tissue homogenate of Dunkin-Hartley guinea pigs by following the decrease in substrate concentration using spectrophotometer. Homogenates of liver were incubated with indole-3-aldehyde in the presence and absence of serotonin or (chlorpromazine and allopurinol a potent and selective inhibitors for aldehyde oxidase and xanthine oxidase, respectively). Oxidation of indole-3-aldehyde to indole-3-acetic acid was reduced up to 63.2% in the presence of serotonin (100 µM), while oxidation of xanthine to uric acid was reduced up to 51.6% under the same conditions. Results: In comparison, incubation of the substrates with their specific inhibitors (100 µM of chlorpromazine and 100 µM allopurinol) give almost complete inhibition. These results demonstrate that in the guinea pig liver a metabolic interaction between serotonin and indole-3-aldehyde or xanthine via molybdenum hydroxylases system may take place in liver, which is the main tissue for xenobiotics detoxification. Conclusion: The overall conclusion from this research is that serotonin could be a protector for neurons and other tissue from the insult of oxidation of aldehydes and xanthines by molybdenum hydroxylases.