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Titolo:
METABOLISM OF CATECHOLAMINES BY CATECHOL-O-METHYLTRANSFERASE IN CELLSEXPRESSING RECOMBINANT CATECHOLAMINE TRANSPORTERS
Autore:
ESHLEMAN AJ; STEWART E; EVENSON AK; MASON JN; BLAKELY RD; JANOWSKY A; NEVE KA;
Indirizzi:
VET AFFAIRS MED CTR,MED RES SERV 15199,3710 SW US VET HOSP RD PORTLAND OR 97201 OREGON HLTH SCI UNIV,DEPT PSYCHIAT PORTLAND OR 97201 OREGON HLTH SCI UNIV,DEPT BEHAV NEUROSCI PORTLAND OR 97201 OREGON HLTH SCI UNIV,DEPT PHYSIOL & PHARMACOL PORTLAND OR 97201 VANDERBILT UNIV,SCH MED,DEPT PHARMACOL NASHVILLE TN 37212 VANDERBILT UNIV,SCH MED,CTR MOL NEUROSCI NASHVILLE TN 37212
Titolo Testata:
Journal of neurochemistry
fascicolo: 4, volume: 69, anno: 1997,
pagine: 1459 - 1466
SICI:
0022-3042(1997)69:4<1459:MOCBCI>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN DOPAMINE TRANSPORTER; METHYL TRANSFERASE; GENE-TRANSFER; CLONING; COCAINE; STRIATUM; LOCALIZATION; INHIBITION; CLEARANCE; RELEASE;
Keywords:
DOPAMINE TRANSPORTER; CDNA; CATECHOL-O-METHYLTRANSFERASE; TROPOLONE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
30
Recensione:
Indirizzi per estratti:
Citazione:
A.J. Eshleman et al., "METABOLISM OF CATECHOLAMINES BY CATECHOL-O-METHYLTRANSFERASE IN CELLSEXPRESSING RECOMBINANT CATECHOLAMINE TRANSPORTERS", Journal of neurochemistry, 69(4), 1997, pp. 1459-1466

Abstract

To determine if catechol-O-methyltransferase (COMT) metabolizes catecholamines within cell lines used for heterologous expression of plasmalemmal transporters and alters the measured characteristics of H-3-substrate transport, the uptake of monoamine transporter substrates was assessed in three cell lines (C6 glioma, L-M fibroblast, and HEK293 cells) that had been transfected with the recombinant human transporters,Uptake and cellular retention of H-3-catecholamines was increased by up to fourfold by two COMT inhibitors, tropolone and Ro 41-0960, with potencies similar to those for inhibition of COMT activity, whereas the uptake of two transporter substrates that are not substrates for COMT, [H-3]serotonin and [H-3]MPP+, was unaffected. Direct measurement ofmonoamine substrates by HPLC confirmed that tropolone (1 mM) increased the retention of the catecholamines dopamine and norepinephrine, butnot the retention of serotonin in HEK293 cells, Saturation analysis of the uptake of [H-3]dopamine by C6 cells expressing the dopamine transporter demonstrated that tropolone (1 mM) decreased the apparent K-m of transport from 0.61 mu M to 0.34 mu M without significantly altering the maximal velocity of transport, These data suggest that endogenous COMT activity in mammalian cells may alter neurotransmitter deposition and thus the apparent kinetic characteristics of transport.

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Documento generato il 05/07/20 alle ore 13:02:00