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Titolo:
ACUTE REGULATION OF NOREPINEPHRINE TRANSPORT - II - PKC-MODULATED SURFACE EXPRESSION OF HUMAN NOREPINEPHRINE TRANSPORTER PROTEINS
Autore:
APPARSUNDARAM S; SCHROETER S; GIOVANETTI E; BLAKELY RD;
Indirizzi:
VANDERBILT UNIV,SCH MED,DEPT PHARMACOL NASHVILLE TN 37232 VANDERBILT UNIV,SCH MED,DEPT PHARMACOL NASHVILLE TN 37232 VANDERBILT UNIV,SCH MED,CTR MOL NEUROSCI NASHVILLE TN 37232
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 2, volume: 287, anno: 1998,
pagine: 744 - 751
SICI:
0022-3565(1998)287:2<744:ARONT->2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN DOPAMINE TRANSPORTER; KINASE-C; XENOPUS-OOCYTES; NORADRENALINE TRANSPORTER; FUNCTIONAL REGULATION; H-3 NISOXETINE; HEK-293 CELLS; RAT-BRAIN; PHOSPHORYLATION; ACTIVATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
40
Recensione:
Indirizzi per estratti:
Citazione:
S. Apparsundaram et al., "ACUTE REGULATION OF NOREPINEPHRINE TRANSPORT - II - PKC-MODULATED SURFACE EXPRESSION OF HUMAN NOREPINEPHRINE TRANSPORTER PROTEINS", The Journal of pharmacology and experimental therapeutics, 287(2), 1998, pp. 744-751

Abstract

Norepinephrine (NE) transporters (NETs) found in the neuronal plasma membrane mediate the removal of NE from the extracellular space, limiting the activation of adrenoceptors at noradrenergic synapses. Our previous studies with the noradrenergic neuroblastoma SK-N-SH have revealed a muscarinic receptor-triggered regulation of NET surface density and transport capacity, mediated in part by protein kinase C activation. Low abundance of NET proteins in this native cell model, however, preclude direct confirmation of altered trafficking of NET proteins. In our study, we monitored the activity and surface distribution of humanNET proteins in transient and stably-transfected cell lines after application of kinase activators and inhibitors. Using hNET stably transfected HEK-293 and LLC-PK1 cells, as well as transiently transfected COS-7 cells, we demonstrate that PKC-activating phorbol esters, beta-PMAor beta-PDBu selectively diminish I-NE transport capacity (Vmax) withlittle change in NE K-m. Effects of phorbol esters are rapid, stereospecific and blocked by protein kinase C inhibitors, staurosporine and bisindolylmaleimide I. As in SK-N-SH cells, beta-PMA induces a reduction in intact cell [H-3]nisoxetine binding sites with no change in nisoxetine K-d or total membrane NET density. Cell-surface biotinylation and confocal immunofluorescence techniques confirm that protein kinase C-dependent reductions in NE transport capacity and whole-cell antagonist binding density are accompanied by reductions in cell-surface human NET protein expression. Together these findings argue for kinase-modulated protein trafficking as a potential route for acute regulation of antidepressant-sensitive NE clearance.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 12:19:51