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Titolo:
Adult human mesangial cells (HMCs) express endothelin-B-receptors which mediate endothelin-1-induced cell growth
Autore:
Orth, SR; Amann, K; Gehlen, F; Unger, L; Wagner, J; Raschack, M; Ritz, E;
Indirizzi:
Univ Heidelberg, Dept Internal Med, Nephrol Sect, D-69115 Heidelberg, Germany Univ Heidelberg Heidelberg Germany D-69115 , D-69115 Heidelberg, Germany Univ Heidelberg, Dept Pathol, D-69115 Heidelberg, Germany Univ HeidelbergHeidelberg Germany D-69115 , D-69115 Heidelberg, Germany Knoll AG, D-6700 Ludwigshafen, Germany Knoll AG Ludwigshafen Germany D-6700 ll AG, D-6700 Ludwigshafen, Germany
Titolo Testata:
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
, volume: 36, anno: 2000, supplemento:, 1
pagine: S232 - S237
SICI:
0160-2446(2000)36:<S232:AHMC(E>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
BINDING-SITES; HUMAN KIDNEY; CALCIUM; RATS;
Keywords:
endothelin (ET); endothelin receptors; mesangial cells; calcium signaling; glomerulosclerosis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
18
Recensione:
Indirizzi per estratti:
Indirizzo: Orth, SR Univ Heidelberg, Dept Internal Med, Nephrol Sect, Bergheimer Str 56A, D-69115 Heidelberg, Germany Univ Heidelberg Bergheimer Str 56A Heidelberg Germany D-69115 ny
Citazione:
S.R. Orth et al., "Adult human mesangial cells (HMCs) express endothelin-B-receptors which mediate endothelin-1-induced cell growth", J CARDIO PH, 36, 2000, pp. S232-S237

Abstract

Endothelin (ET) receptor antagonists are nephroprotective in renal damage models of the rat. It is unknown whether ET receptor antagonists are also beneficial in human renal diseases. Major differences exist between the ET systems in rats and humans, therefore this study was designed to characterize the ET receptors expressed on human adult mesangial cells (HMCs). HMCs cultures are a surrogate model for the development of glomerulosclerosis. Binding experiments with [I-125]ET-1 in the presence or the absence of the test compounds [endothelin-1, -3 (ET-1, ET-3), sarafotoxin 6c (S6c), or BQ123]revealed an affinity (IC50 values) of 10.5 nm for ET-1 and 87.6 nm for ET-3. The affinities of the ETB agonist S6c and the ETA antagonist BQ123 were 85.9 nm and > 10 mum, respectively. Thus, the ET receptor on HMCs shows an ETB-like pharmacology, but in contrast to the classical ETB-receptor the affinities are low. No affinity for BQ123 up to > 10 mum excludes the presence of ETA-receptors. Functional studies using microfluorimetry (fura-2 method) showed comparable biphasic calcium signals induced by 10 nm ET-1, ET-3 and S6c. This effect could not be inhibited by BQ123, but by the ETB antagonist BQ788. Reverse transcriptase polymerase chain reaction (RT-PCR) studiesunder different culture conditions showed that both ETA- and ETB-receptor mRNAs are expressed in HMCs. The amount of ETA-receptor mRNA increased 2.7-fold and that of the ETB-receptor mRNA 7.1-fold after stimulation with 10% fetal calf serum (FCS). ET-1, ET-3 and S6c stimulated HMCs growth (ET-1 > S6c > ET-3), but the magnitude of the effect of ET-1 is lower than reported in rat mesangial cells (rat MCs). The effect on HMCs growth could be inhibited by BQ788, but not by BQ123. Our data provide evidence for the expression of ETB-receptors on HMCs that are functionally active. This finding differs from the ET receptor expression in rat MCs as reported by others.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 07:37:04