ngs are thought to be formed by condensation between dopamine and certain metabolites of ethanol, organic solvents and anesthetic gases. Described here are experiments aimed at evaluating ngs interference with catecholamine synthesis. Rat adrenal pheochromocytoma (PC 12) cell lysates were exposed to benzyl-TIQ and phenyl-TlQ. The activities of tyrosine hydroxylases (TH) and dopamine beta-hydroxylase (DBH) were measured by HPLC-based methods following exposure to variable concentrations of TlQs. The effects of TlQs on DBH activity were also assessed in human serum. Dixon plot analyses revealed that TlQs act on TH as competitive inhibitors with different affinity. Ki for benzyl- and phenyl-TlQ were 5 and 3 mu M respectively. DBH activity in serum exposed to benzyl- and phenyl-TlQ ranging from 0.2 to 20 mu M rose respectively by 12.5% to 58% for benzyl- and by 7.8% to 26% for phenyl-TlQ. Such ngs interferences with catecholamine metabolism seem to account for dopamine (DA) depletion observed in parallel in vitro experiments on PC12 cells. The dose-dependent inhibition of TH and the increased activity of DBH together with the relatively low effective doses of ngs suggest this mechanism as a possible explanation of the selective toxicity of styrene and other solvents to dopaminergic systems observed in rabbits following experimental exposure and suspected to occur in occupationally-exposed workers

MULTIPLE INTERFERENCES ON CATECHOLAMINE METABOLISM BY TETRAHYDROISOQUINOLINES (TIQS) / A., Smargiassi; C., Biagini; Mutti, Antonio; Bergamaschi, Enrico; A., Bacchini; R., Alinovi; S., Cavazzini. - In: NEUROTOXICOLOGY. - ISSN 0161-813X. - 15:(1994), pp. 765-768. (Intervento presentato al convegno 4th Meeting of the International-Neurotoxicology-Association tenutosi a ELSINORE, DENMARK nel JUN 06-11, 1993).

MULTIPLE INTERFERENCES ON CATECHOLAMINE METABOLISM BY TETRAHYDROISOQUINOLINES (TIQS)

MUTTI, Antonio;BERGAMASCHI, Enrico;
1994-01-01

Abstract

ngs are thought to be formed by condensation between dopamine and certain metabolites of ethanol, organic solvents and anesthetic gases. Described here are experiments aimed at evaluating ngs interference with catecholamine synthesis. Rat adrenal pheochromocytoma (PC 12) cell lysates were exposed to benzyl-TIQ and phenyl-TlQ. The activities of tyrosine hydroxylases (TH) and dopamine beta-hydroxylase (DBH) were measured by HPLC-based methods following exposure to variable concentrations of TlQs. The effects of TlQs on DBH activity were also assessed in human serum. Dixon plot analyses revealed that TlQs act on TH as competitive inhibitors with different affinity. Ki for benzyl- and phenyl-TlQ were 5 and 3 mu M respectively. DBH activity in serum exposed to benzyl- and phenyl-TlQ ranging from 0.2 to 20 mu M rose respectively by 12.5% to 58% for benzyl- and by 7.8% to 26% for phenyl-TlQ. Such ngs interferences with catecholamine metabolism seem to account for dopamine (DA) depletion observed in parallel in vitro experiments on PC12 cells. The dose-dependent inhibition of TH and the increased activity of DBH together with the relatively low effective doses of ngs suggest this mechanism as a possible explanation of the selective toxicity of styrene and other solvents to dopaminergic systems observed in rabbits following experimental exposure and suspected to occur in occupationally-exposed workers
1994
MULTIPLE INTERFERENCES ON CATECHOLAMINE METABOLISM BY TETRAHYDROISOQUINOLINES (TIQS) / A., Smargiassi; C., Biagini; Mutti, Antonio; Bergamaschi, Enrico; A., Bacchini; R., Alinovi; S., Cavazzini. - In: NEUROTOXICOLOGY. - ISSN 0161-813X. - 15:(1994), pp. 765-768. (Intervento presentato al convegno 4th Meeting of the International-Neurotoxicology-Association tenutosi a ELSINORE, DENMARK nel JUN 06-11, 1993).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2435153
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