Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Differential abilities of phorbol esters in inducing protein kinase C (PKC) down-regulation in noradrenergic neurones
Autore:
Kotsonis, P; Funk, L; Prountzos, C; Iannazzo, L; Majewski, H;
Indirizzi:
RMIT Univ, Dept Med Lab Sci, Melbourne, Vic 3001, Australia RMIT Univ Melbourne Vic Australia 3001 ci, Melbourne, Vic 3001, Australia Univ Freiburg Klinikum, Abt Innere Med 4, D-79106 Freiburg, Germany Univ Freiburg Klinikum Freiburg Germany D-79106 -79106 Freiburg, Germany Novartis Inst Med Sci, London WC1E 6BN, England Novartis Inst Med Sci London England WC1E 6BN , London WC1E 6BN, England
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 2, volume: 132, anno: 2001,
pagine: 489 - 499
SICI:
0007-1188(200101)132:2<489:DAOPEI>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEPENDENT NEUTRAL PROTEASE; RAT-BRAIN CORTEX; NEUROTRANSMITTER RELEASE; STRUCTURAL REQUIREMENTS; PHOSPHOLIPID-VESICLES; NEUROBLASTOMA-CELLS; PHOSPHORYLATION; ACTIVATION; BINDING; NORADRENALINE;
Keywords:
protein kinase C (PKC); PKC down-regulation; phorbol esters; noradrenaline release; phosphorylation; B-50; brain cortex;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Majewski, H RMIT Univ, Dept Med Lab Sci, GPO Box 2476V, Melbourne, Vic 3001, Australia RMIT Univ GPO Box 2476V Melbourne Vic Australia 3001 Australia
Citazione:
P. Kotsonis et al., "Differential abilities of phorbol esters in inducing protein kinase C (PKC) down-regulation in noradrenergic neurones", BR J PHARM, 132(2), 2001, pp. 489-499

Abstract

1 The ability of several phorbol ester protein kinase C (PKC) activators (phorbol 12, 13-dibutyrate, PDB, phorbol 12, 13-diacetate, PDA, and 12-deoxyphorbol 13-acetate, dPA) to downregulate PKC was studied by assessing theireffects on electrical stimulation-induced (S-T) noradrenaline release fromrat brain cortical slices and phosphorylation of the PKC neural substrate B-50 in rat cortical synaptosomal membranes.2 In cortical slices which were incubated for 20 h with vehicle, acute application of PDB, PDA and dPA (0.1-3.0 muM) enhanced the S-I noradrenaline release in a concentration-dependent manner to between 200-250% of control in each case. In slices incubated with PDB (1 muM for 20 h), subsequent acute application of PDB (0.1-3.0 muM) failed to enhance S-I release, indicating PKC down-regulation. However, in tissues incubated with PDA or dPA (3 muM) for 20 h, there was no reduction in the facilitatory effect of their respective phorbol esters or PDB (0.1-3.0 muM) when acutely applied, indicatingthat PKC was not down-regulated. This was confirmed using Western blot analysis which showed that PDB (1 muM for 20 h) but not PDA (3 muM for 20 h) caused a significant reduction in PKC alpha.3 Incubation with PDB for 20 h, followed by acute application of PDB (3 muM) failed to increase phosphorylation of B-50 in synaptosomal membranes, indicating down-regulation. In contrast, tissues incubated with PDA or dPA for 20 h, acute application of their respective phorbol ester (10 muM) Or PDB(3 muM) induced a significant increase in B-50 phosphorylation.4 Acutely all three phorbol esters elevate noradrenaline release to about the same extent, yet PDA and dPA have lower affinities for PKC compared to PDB, suggesting unique neural effects for these agents. This inability to cause functional down-regulation of PKC extends their unusual neural properties. Their neural potency and lack of down-regulation may be related to their decreased lipophilicity compared to other phorbol esters.5 We suggest that PKC down-regulation appears to be related to binding affinity, where agents with high affinity, irreversibly insert PKC into artificial membrane lipid and generate Ca2+-independent kinase activity which degrades and deplete PKC. We suggest that this mechanism may also underlie theability of PDB to down-regulate PKC in nerve terminals, in contrast to PDAand dPA.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 22:18:04