Katsuyuki Miura (1), Michiaki Okumura (2), Shinya Yamanaka (1), Shokei
Kim (1) and Hiroshi Iwao (1)
(1) Department of Pharmacology, Osaka City University Medical School,
1-4-3 Asahimachi, Abeno, Osaka 545-8585, Japan
(2) Department of Internal Medicine, Osaka City General Hospital, 2-13-22,
Miyakojima-Hondori, Miyakojima, Osaka 534-0021, Japan
Abstract: Intrarenal infusion of 4-pentenoic acid is known to
lower renal cortical ATP content and cause a reduction in glomerular filtration
rate (GFR). The alteration in nucleotide metabolism might augment the production
of adenosine, thereby eliciting the fall in GFR. This study was conducted
to examine whether 4-pentenoic acid stimulates renal production of adenosine,
and if so, to examine the role of adenosine A1 receptor in the reduction
of GFR by 4-pentenoic acid. With infusion of 4-pentenoic acid (1 micromolEkg-1Emin-1)
into the renal artery of anesthetized dogs, GFR gradually decreased and
reached minimum at 60 min with values ranging from 33.9 +/-2.2 to 20.2+/-2.8
ml/min. Neither renal blood flow nor mean arterial pressure was affected,
but tubular reabsorption of water and sodium was significantly attenuated.
Renal venous plasma concentration and urinary excretion of adenosine rose
markedly (20-fold) without any change in arterial concentration, suggesting
that renal adenosine production was augmented by 4-pentenoic acid. However,
KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), a selective antagonist
of the adenosine A1 receptor, did not affect the action of 4-pentenoic acid
on GFR or renal handling of water and sodium. It is concluded that 4-pentenoic
acid markedly increases renal adenosine production, but adenosine A1 receptor
is not involved in the 4-pentenoic acid-induced nephrotoxicity.
Keywords: Adenosine, Renal, 4-Pentenoic acid, Glomerular filtration rate
CopyrightŠ The Japanese Pharmacological Society 1999
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