No Participation of Adenosine A1 Receptor in Acute Nephrotoxicity by 4-Pentenoic Acid Administration in Dogs

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 micromol x kg(-1) x min(-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.