Detrimental subtype-specific endothelin-1 (ET-1) signaling in myocardial cells: the ET(A) mediated proliferation and ET(B) receptor down-regulation

Title:

Detrimental subtype-specific endothelin-1 (ET-1) signaling in myocardial cells: the ET(A) mediated proliferation and ET(B) receptor down-regulation

Creator:

Ján Dřímal, Mislovičová, M., Ismail, A., and Monček, F.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:bd3d643c-dbfa-4afe-9e52-1caa58a58902
uuid:bd3d643c-dbfa-4afe-9e52-1caa58a58902
issn:0862-8408

Subject:

Fyziologie člověka a srovnávací fyziologie, fyziologie, physiology, ligand binding, endothelin-1, photoaffinity labeling, Ca2+ channels, human fibroblasts, porcine myocardium, microsomal membranes, rat renal hypertension, 14, and 612

Type:

article, články, model:article, and TEXT

Format:

print, bez média, and svazek

Description:

Many physiological and pathological processes in the cardiac tissue have been shown to be associated with a release of endothelin (ET) peptides and with induction of specific ET-receptors and G-protein-coupled ion channels. However, the exact mechanism regulating ET-receptors in the myocardium is controversial. The response to ET-1, the most important member of the ET family, is rapidly attenuated by down-regulation of ET-receptors. The internalization of ET-1 bound to two subclasses of specific receptors (ETA and ETB) that are abundant in the myocardium has been hypothesized to activate and/or inhibit a variety of intracellular signal transducing systems. The [125I]ET-1, BQ-3020 and selective ET-antagonists were used to study the subtype-selective component of regulation of ET-1 receptors in myocardial membranes. We determined the characteristics of [125I]ET-1 binding and [3H]thymidine incorporation in whole cell saturation studies and measured Ca 2+ channel induction and the total number of inactive Ca2+ channels in photoaffinity studies with [3H]azidopine. Here we demonstrate four important components of the complex ET-1 response in human, porcine and rat myocardium, leading to aberrant responses of cells. After ET-1 induction, adaptive subtype-ETB selective down-regulation predominated in human embryonic fibroblasts, in porcine membrane vesicles and in microsomal membranes of renal hypertensive rats, with preferential high affinity ET-1 binding to ETA receptors and with the resultant ETA mediated proliferative and mitogenic activation of human fibroblasts. The ET-1 induction was also accompanied by profound inactivation of Ca2+ channels in myocardial membranes., J. Dřímal, M. Mislovičová, A. Ismail, F. Monček., and Obsahuje bibliografii

Language:

English

Rights:

http://creativecommons.org/licenses/by-nc-sa/4.0/
policy:public

Source:

Physiological research | 1999 Volume:48 | Number:1

Harvested from:

CDK

Metadata only:

false