Formation and clearance of interstitial metabolites of dopamine and serotonin in the rat striatum: an in vivo microdialysis study.

作者: Paul Cumming , Erin Brown , Geert Damsma , Hans Fibiger

DOI: 10.1111/J.1471-4159.1992.TB11026.X

关键词:

摘要: : In vivo microdialysis was employed in order to characterize the steady-state kinetics of turnover specific dopamine and serotonin metabolites rat striaturn 48 h after surgery. Inhibitors monoamine oxidase (MAO; pargyline) catechol-O-methyltransferase (COMT; Ro 40-7592) were administered, either separately or conjunction, at doses sufficient block these enzymes CNS. some experiments, acid metabolite carrier blocked with probenecid. Temporal changes then observed efflux interstitial dopamine, 3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic (DOPAC), homovanillic (HVA), 5-hydroxyindoleacetic (5-HIAA). The fractional rate constants for accumulation disappearance could be determined pharmacological blockade catabolic carrier. Interstitial 5-HIAA found cleared a half-life approximately 2 h. After MAO COMT, HVA disappeared 17 min. Experiments employing probenecid suggested that by carrier, remainder being probenecid-insensitive process, possibly conjugation. inhibition, DOPAC an apparent 11.3 3-MT pargyline indicated majority (>95%) is formed from rather than 3-MT. formation calculated pargyline, appeared follow first-order (k = 0.1 min−1).

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