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Titolo:
Urocortin, but not corticotropin-releasing hormone (CRH), activates the mitogen-activated protein kinase signal transduction pathway in human pregnant myometrium: An effect mediated via R1 alpha and R2 beta CRH receptor subtypes and stimulation of Gq-proteins
Autore:
Grammatopoulos, DK; Randeva, HS; Levine, MA; Katsanou, ES; Hilhouse, EW;
Indirizzi:
Univ Warwick, Dept Biol Sci, Sir Quinton Hazell Mol Med Res Ctr, Coventry CV4 7AL, W Midlands, England Univ Warwick Coventry W Midlands England CV4 7AL 7AL, W Midlands, England Johns Hopkins Univ, Sch Med, Div Pediat Endocrinol, Baltimore, MD 21287 USA Johns Hopkins Univ Baltimore MD USA 21287 crinol, Baltimore, MD 21287 USA Johns Hopkins Univ, Sch Med, Dept Pediat, Ilyssa Ctr Cellular & Mol Endocrinol, Baltimore, MD 21287 USA Johns Hopkins Univ Baltimore MD USA 21287 crinol, Baltimore, MD 21287 USA
Titolo Testata:
MOLECULAR ENDOCRINOLOGY
fascicolo: 12, volume: 14, anno: 2000,
pagine: 2076 - 2091
SICI:
0888-8809(200012)14:12<2076:UBNCH(>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
PUERPERAL UTERINE CONTRACTION; MAP KINASE; LIGAND-BINDING; HUMAN-PLACENTA; PROSTAGLANDIN PRODUCTION; DIFFERENTIAL REGULATION; EXTRACELLULAR DOMAIN; FETAL MEMBRANES; PC12 CELLS; RAT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Grammatopoulos, DK Univ Warwick, Dept Biol Sci, Sir Quinton Hazell Mol MedRes Ctr, Gibbet Hill Rd, Coventry CV4 7AL, W Midlands, England Univ Warwick Gibbet Hill Rd Coventry W Midlands England CV4 7AL
Citazione:
D.K. Grammatopoulos et al., "Urocortin, but not corticotropin-releasing hormone (CRH), activates the mitogen-activated protein kinase signal transduction pathway in human pregnant myometrium: An effect mediated via R1 alpha and R2 beta CRH receptor subtypes and stimulation of Gq-proteins", MOL ENDOCR, 14(12), 2000, pp. 2076-2091

Abstract

CRH and CRH-related peptides such as urocortin mediate their actions in the human myometrium via activation of two distinct classes of CRH receptors,R1 and R2. These heptahelical receptors are able to stimulate a number of different intracellular signals; one key mediator of G protein-activated intracellular signaling is the cascade of p42/p44, mitogen-activated protein kinase (MAPK). We therefore hypothesized that activation of MAPK might mediate CRH and or/urocortin actions in the myometrium. In cultured human pregnant myometrial cells, urocortin but not CRH was able to induce MARK phosphorylation and activation, suggesting that in the human myometrium these two peptides have distinct actions and biological roles. To identify the particular receptor subtypes mediating this phenomenon, all known CRH receptors present in the human myometrial cells were stably expressed individually in HEK293 and CHO cells, and their ability to activateMAPK was tested. The R1 alpha and R2 beta, but not the R1 beta, R1c, or R1d, receptor subtypes were able to mediate urocortin-induced MAPK activation. The signaling components were further investigated; activation of Gs, Go,or Gi proteins did not appear to be involved, but activation of Gq with subsequent production of inositol triphosphates (IP3) and protein kinase C (PKC) activation correlated with MARK phosphorylation. Studies on Gq protein activation using [alpha-P-32]-GTP-gamma -azidoanilide and IP3 production incells expressing the R1 alpha or R2 beta CRH receptors demonstrated that urocortin was 10 times more potent than CRH. Moreover, urocortin (UCN) generated peak responses that were 50-70% greater than CRH in activating the Gq protein and stimulating IP3 production. In conclusion, UCN acting thought multiple receptor subtypes can stimulatemyometrial MAPK via induction of the Gq/phospholipase C/IP3/PKC pathway, whereas CRH-induced activation of this pathway appears to be insufficient toachieve MAPK activation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 07:28:16