ANG II-mediated inhibition of neuronal delayed rectifier K+current: role of protein kinase C-α

Autor:	Mohan K. Raizada, Mingyan Zhu, Craig H. Gelband, Sheng-Jun Pan, Colin Sumners
Rok vydání:	2001
Předmět:	medicine.medical_specialty Physiology Kinase Chemistry Endogeny Cell Biology Angiotensin II Molecular biology chemistry.chemical_compound Endocrinology Chelerythrine medicine.anatomical_structure Internal medicine medicine Neuron Signal transduction Protein kinase C Diacylglycerol kinase
Zdroj:	American Journal of Physiology-Cell Physiology. 281:C17-C23
ISSN:	1522-1563 0363-6143
DOI:	10.1152/ajpcell.2001.281.1.c17
Popis:	It was previously determined that ANG II and phorbol esters inhibit Kv current in neurons cultured from newborn rat hypothalamus and brain stem in a protein kinase C (PKC)- and Ca2+-dependent manner. Here, we have further defined this signaling pathway by investigating the roles of “physiological” activators of PKC and different PKC isozymes. The cell-permeable PKC activators, diacylglycerol (DAG) analogs 1,2-dioctanoyl- sn-glycerol (1 μmol/l, n = 7) and 1-oleoyl-2-acetyl- sn-glycerol (1 μmol/l, n = 6), mimicked the effect of ANG II and inhibited Kv current. These effects were abolished by the PKC inhibitor chelerythrine (1 μmol/l, n = 5) or by chelation of internal Ca2+( n = 8). PKC antisense (AS) oligodeoxynucleotides (2 μmol/l) against Ca2+-dependent PKC isoforms were applied to the neurons to manipulate the endogenous levels of PKC. PKC-α-AS ( n = 4) treatment abolished the inhibitory effects of ANG II and 1-oleoyl-2-acetyl- sn-glycerol on Kv current, whereas PKC-β-AS ( n = 4) and PKC-γ-AS ( n = 4) did not. These results suggest that the angiotensin type 1 receptor-mediated effects of ANG II on neuronal Kv current involve activation of PKC-α.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::ee95a1eca92233f56ac0a180873c1761 https://doi.org/10.1152/ajpcell.2001.281.1.c17 Zobrazit plný text záznamu