Up-regulated renal proximal adenosine a1 receptor is associated
with augmented pkc and glucose transport but inhibited
proliferation.
Coulson, Richard, Paula S. Proch, Ray A. Olsson, Charles E. Chalfant,
and Denise R. Cooper.
Department of Veterans Affairs, James A. Haley Veterans Hospital,
Tampa, Florida 33612; Departments of Internal Medicine and
Biochemistry, University of South Florida, Tampa, Florida 33620
APStracts 2:0134F, 1995.
Adenosine A1-receptor densities were increased in cultured LLC-PK1 or
OK cells by chronic treatment with the adenosine receptor
antagonists: 1,3,7-trimethylxanthine (caffeine; 1mM) or 1,3-dimethyl
-8-cyclopentylxanthine (cyclopentyltheophylline or CPT; /=0.1
mM) inhibited cell proliferation for the first 10 days, then cell
growth assumed a normal proliferative rate despite continued presence
of antagonist. Both cytosolic protein kinase C (PKC) isoform
immunoactivity and PKC II mRNA were elevated at least 2-fold during
10 days of 0.1 mM CPT or 1 mM caffeine treatment. The sustained
elevation in Na-glucose symport and PKC activity observed with
adenosine receptor antagonists was similar to acute (2h) effects of
adenosine A1 agonist R-PIA (0.1-1 [mu]M). Moreover, cell
proliferation was increased by adenosine (0.1 [mu]M R-PIA) whereas
Na,K-ATPase activity was unaltered with either chronic antagonist or
acute adenosine treatments. Caffeine treatment may have some non
-adenosine A1 receptor-mediated actions since it slightly (30%)
augmented PKA activity. It is concluded that chronic exposure of
proximal tubule cells to caffeine or CPT augments PKC and sodium
-glucose transport but retards cell proliferation mainly via adenosine
A1 receptor-mediated mechanisms.
Received 24 January 1995; accepted in final form 31 July 1995.
APS Manuscript Number F23-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.