Production and Effects of Endothelin-1 in Rat Pancreatic Stellate Cells

Autor: Roland Reinehr, Ulrich Warskulat, Reinhard Lüthen, Dieter Häussinger, Richard Fischer, Hanne Klonowski-Stumpe
Rok vydání: 2003
Předmět:
Zdroj: Pancreas. 27:67-74
ISSN: 0885-3177
DOI: 10.1097/00006676-200307000-00010
Popis: Introduction: Proliferation and matrix synthesis of activated pancreatic stellate cells (PSCs) participate in the development of chronic pancreatitis. Besides other substances, endpthelin-1 (ET-1) may influence the activation process of PSCs. Until now, ET-1 has not been studied in this particular cell type. Aims: To characterize PSCs in rat pancreas with respect to expression of ET A -receptors, production of ET-1, and physiological effects induced by ET-1 during PSC activation. Methodology: Immunocytochemical and ELISA techniques and cDNA microarray analysis were used. Physiologic effects were characterized by single cell measurements of free cytosolic Ca 2+ -concentration and of PSC contractility on collagen lattices. Results: Activation of PSCs in vitro, as assessed by α-smooth muscle actin expression, was accompanied by the de novo expression of ET A -receptors and synthesis of ET- I mRNA and protein. Cytosolic Ca 2+ -concentration was increased upon ET-1 stimulation in activated but not in quiescent PSCs. Contractility of activated PSCs was significantly reduced by the selective ET A -receptor antagonist BQ123 but not by the ET B -receptor antagonist IRL-1038. Conclusions: The results suggest that ET-1 may act as a paracrine and autocrine factor for activated PSCs and may mediate contractions of activated, but not quiescent, PSCs.
Databáze: OpenAIRE