Rat proximal tubule cell line transformed with origin-defective
sv40 dna: autocrine angiotensin ii feedback.
Ingelfinger, Julie R., Flavia Jung, Daniel Diamant, Liam Haveran,
Edwin Lee, Andrew Brem and Shiow-Shih Tang.
1Pediatric Nephrology Laboratory, Massachusetts General Hospital,
Harvard Medical School, Boston, MA 02114 and 2Rhode Island Hospital,
Brown University, Providence, Rhode Island 02903
APStracts 5:0175F, 1998.
The renal proximal tubule is a major site for a complete tissue renin
angiotensin system (RAS) and produces endogenous angiotensin II (Ang
II). The present studies demonstrate autocrine RAS feedback in a line
of origin-defective SV40 plasmid transformed immortalized rat
proximal tubular cells (IRPTC) designated as line 93-p-2-1, that are
highly differentiated and express all RAS components. Receptor
competition assays and southern blot following RT-PCR demonstrated
that these IRPTC express AT1 and AT2 angiotensin receptor subtypes.
Autocrine RAS feedback was examined following exposure to Ang II (10
-8 M): angiotensinogen mRNA increases significantly by 1 hour and
remains elevated through 24 hours. The AT1 blocker losartan prevents
this increase. Moreover, Ang II upregulates expression of Ang II
receptor mRNA (both AT1 and AT2). Thus, the present studies
demonstrate positive Ang II feedback with angiotensinogen and Ang II
receptors in proximal tubule cells, suggesting that the main site of
such intrarenal feedback in vivo is within proximal tubule. Ang II
secreted by line 93-p-2-1 is increased by isoproterenol, suggesting
b-adrenergic regulation in IRPTC.
Received 14 October 1997; accepted in final form 1 October 1998.
APS Manuscript Number F331-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 20 October 1998