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Titolo:
Acute inhibition of brain-specific Na+/H+ exchanger isoform 5 by protein kinases A and C and cell shrinkage
Autore:
Attaphitaya, S; Nehrke, K; Melvin, JE;
Indirizzi:
Univ Rochester, Med Ctr, Sch Med & Dent, Aab Inst Biomed Sci,Ctr Oral Biol, Rochester, NY 14642 USA Univ Rochester Rochester NY USA 14642 Oral Biol, Rochester, NY 14642 USA Univ Rochester, Sch Med & Dent, Dept Dent, Rochester, NY 14642 USA Univ Rochester Rochester NY USA 14642 Dept Dent, Rochester, NY 14642 USA Univ Rochester, Sch Med & Dent, Dept Neurobiol & Anat, Rochester, NY 14642USA Univ Rochester Rochester NY USA 14642 biol & Anat, Rochester, NY 14642USA
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
fascicolo: 4, volume: 281, anno: 2001,
pagine: C1146 - C1157
SICI:
0363-6143(200110)281:4<C1146:AIOBNE>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT NA/H EXCHANGER; HAMSTER OVARY CELLS; INTRACELLULAR PH REGULATION; MOLECULAR-CLONING; FUNCTIONAL EXPRESSION; TARGETED DISRUPTION; ACID EXTRUSION; ATP DEPENDENCE; NHE3 ACTIVITY; CA1 NEURONS;
Keywords:
pH regulation; amiloride; sodium-proton exchange; sodium/hydrogen;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Melvin, JE Univ Rochester, Med Ctr, Sch Med & Dent, Aab Inst Biomed Sci,Ctr Oral Biol, Box 611,601 Elmwood Ave, Rochester, NY 14642 USA Univ Rochester Box 611,601 Elmwood Ave Rochester NY USA 14642 A
Citazione:
S. Attaphitaya et al., "Acute inhibition of brain-specific Na+/H+ exchanger isoform 5 by protein kinases A and C and cell shrinkage", AM J P-CELL, 281(4), 2001, pp. C1146-C1157

Abstract

Little is known of the functional properties of the mammalian, brain-specific Na+/H+ exchanger isoform 5 (NHE5). Rat NHE5 was stably expressed in NHE-deficient PS120 cells, and its activity was characterized using the fluorescent pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. NHE5 was insensitive to ethylisopropyl amiloride. The transport kinetics displayed a simple Michaelis-Menten relationship for extracellular Na+ (apparent K-Na = 27 +/- 5 mM) and a Hill coefficient near 3 for the intracellular proton concentration with a half-maximal activity at an intracellular pH of6.93 +/- 0.03. NHE5 activity was inhibited by acute exposure to 8-bromo-cAMP or forskolin (which increases intracellular cAMP by activating adenylatecyclase). The kinase inhibitor H-89 reversed this inhibition, suggesting that regulation by cAMP involves a protein kinase A (PKA)-dependent process. In contrast, 8-bromo-cGMP did not have a significant effect on activity. The protein kinase C (PKC) activator phorbol 12-myristrate 13-acetate inhibited NHE5, and the PKC antagonist chelerythrine chloride blunted this effect. Activity was also inhibited by hyperosmotic-induced cell shrinkage but was unaffected by a hyposmotic challenge. These results demonstrate that rat brain NHE5 is downregulated by activation of PKA and PKC and by cell shrinkage, important regulators of neuronal cell function.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 10:56:44