Enhanced endothelin ET(B) receptor down-regulation in human tumor cells
| Autor: | Jan Drimal, Daniel Drimal |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
Endothelin receptor type A medicine.drug_class Down-Regulation Ligands Internal medicine Neoplasms medicine Humans Receptor Cells Cultured Pharmacology Membranes Endothelin-1 Chemistry Endothelin receptor antagonist Receptors Endothelin Endothelins Antagonist Protein kinase inhibitor Fibroblasts Receptor antagonist Endothelin 1 Receptor Endothelin B Peptide Fragments Kinetics Endocrinology cardiovascular system Endothelin receptor HeLa Cells |
| Zdroj: | European journal of pharmacology. 396(1) |
| ISSN: | 0014-2999 |
| Popis: | The characteristics of specific binding of human [ 125 I]Tyr 13 -endothelin-(1–21), [ 125 I]-Tyr 13 -Suc-[Glu 9 ,Ala 11,15 ]-endothelin-(8–21), ([ 125 I]IRL-1620) and endothelin ET A receptor antagonist [ 125 I]Tyr 3 -( N -[(hexahydro-1 H -azepin-1-yl)carbonyl]- l -Leu]-1Me)- d -Trp ([ 125 I]PD151242) (number of sites and their affinity) and proliferation responses to exogenous endothelin receptor agonists (endothelin-1 and the endothelin ET B receptor-selective, truncated N -acetyl-[Ala 11,15 ]-endothelin-(6–21) analogue BQ3020) were determined in cultured human fibroblasts and in tumorigenic HeLa cells. The cells were pre-incubated with equimolar concentrations of human endothelin-1 or its truncated analogue BQ3020. After pre-incubation (2 h), both peptides induced down-regulation of surface-membrane endothelin-1 receptors. This process was specific for endothelin ET B receptors and was much more intensive in tumorigenic cells. BQ3020, acting mostly through its C-terminus, induced nearly maximal endothelin ET B receptor down-regulation in HeLa cells. Staurosporine, a wide spectrum protein kinase inhibitor, significantly reduced, and N -[ N -[ N -[2,6-dimethyl-1piperidinyl)carbonyl]-4-Me- l- Leu]-1-(methoxycarbonyl)- d -tryptophanyl]- d -norleucine (BQ788), an endothelin ET B receptor antagonist, attenuated the down-regulation of endothelin receptors induced by endothelin receptor agonists. The down-regulation of endothelin ET B receptors was prevented by pre-incubation of the cells with the lysosomal enzyme blocker chloroquine. The endothelin-1-induced cell proliferation was attenuated by pre-incubation of the cells with the non-selective endothelin receptor antagonist Ac- d -10,11-dihydro-5 H -dibenzo[ a , d ] cycloheptene-glycine-3,3- d -diphenyl-Ala-Leu-Asp-Ile-Ile-Trp (PD142893) and it was only partially reduced by the endothelin ET A receptor-selective endothelin antagonist PD151242. |
| Databáze: | OpenAIRE |
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