Effects of angiotensin II on rat pancreatic stellate cells.
The aim of the study was to identify pancreatic stellate cells (PSCs) as a potential target of angiotensin II (ATII) action because recently a local renin-angiotensin system (RAS) has been described in the pancreas. PSCs were isolated from male Wistar rats and investigated for ATII receptor expression and ATII-induced calcium transients, contractions, proliferation, and alpha-smooth muscle actin expression. Quiescent and activated PSCs expressed the ATII receptor subtype AT1 but not AT2. Addition of ATII led to a rapid elevation of intracellular calcium ([Ca]i). The sensitivity toward ATII with respect to calcium transients did not change during the transdifferentiation process. In activated PSCs, ATII dose dependently induced PSC cell contraction. Furthermore, ATII induced an activation of the c-Jun-N-terminal kinase (JNK) and extracellular regulated kinase (Erk), which was inhibited after intracellular calcium chelation by BAPTA-AM. The p38 mitogen-activated protein kinase (p38) was also activated by ATII. BAPTA-AM itself induced p38 activation, which was not further enhanced by ATII. ATII stimulated PSC proliferation, while PSC transdifferentiation, as indicated by alpha-smooth muscle actin expression and collagen type I secretion, was not enhanced. The data suggest that PSCs are targets of ATII action with potential pathophysiological relevance.
Reinehr
Roland
R
Clinic for Gastroenterology, Hepatology, and Infectiology, Heinrich-Heine-University, Düsseldorf, Germany.
Zoller
Stefan
S
Klonowski-Stumpe
Hanne
H
Kordes
Claus
C
Häussinger
Dieter
D
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010179:Pancreas / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000378:metabolism
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D020929:Mitogen-Activated Protein Kinase Kinases; D002118:Calcium