Tsutomu Yonehana and Munekazu Gemba (*)
Division of Pharmacology, Osaka University of Pharmaceutical Sciences,
Nasahara, Takatsuki, Osaka 569-1094, Japan
(*) To whom correspondence should be addressed.
Abstract: We studied the effects of adenosine on injury caused
by hypoxia and reoxygenation in LLC-PK1 cells. Lactate dehydrogenase
and gamma-glutamyltranspeptidase were released from cells exposed to hypoxia
for 6 hr and then reoxygenation for 1 hr. The addition of adenosine at 100
microM to the medium before hypoxia began significantly decreased enzyme
leakage into medium during both hypoxia and reoxygenation. The adenosine
A1-receptor agonist, R(-)-N6-(2-phenylisopropyl)adenosine
(R-PIA), at the concentration of 100 microM, did not affect enzyme release,
but the adenosine A2-receptor agonist 2-p-[2-carboxyethyl]phenethyl-amino-5'-N-ethylcarboxamido-adenosine
hydrochloride (CGS 21680) at the concentration of 100 microM, suppressed
the injury caused by hypoxia and reoxygenation. There were decreases in
cAMP contents and ATP levels in LLC-PK1 cells injured by hypoxia
and reoxygenation. Adenosine (100 nM) restored ATP levels in the cells during
reoxygenation. With adenosine, the intracellular cAMP level was increased
prominently during reoxygenation. These results suggest that adenosine protects
LLC-PK1 cells from injury caused by hypoxia and reoxygenation
by increasing the intracellular cAMP level via adenosine A2 receptor.
Keywords: Acute renal failure, Hypoxia and reoxygenation, Adenosine A2
receptor, Cyclic AMP, LLC-PK1 cell