The role of adenosine in glycine-induced glomerular hyperfiltration in rats.
Ingestion of a high-protein diet or infusion of amino acids induces glomerular hyperfiltration and hyperemia. We have investigated the role of endogenous adenosine in glycine-induced hyperfiltration. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured in conscious chronically instrumented rats. Glycine (3.7 mg/min, i.v.; n = 6) significantly increased GFR and ERPF from 0.92 +/- 0.07 to 1.13 +/- 0.08 and 3.28 +/- 0.24 to 3.69 +/- 0.19 ml/min.100 g, respectively. In the presence of adenosine deaminase (ADA, 2 U/kg.min, n = 6), glycine-induced glomerular hyperfiltration and hyperemia were blunted. The small changes in GFR (from 0.86 +/- 0.06 to 0.90 +/- 0.10 ml/min.100 g) and ERPF (from 3.60 +/- 0.57 to 3.83 +/- 0.53 ml/min x 100 g) were not statistically significant. Erythro-9-(2-hydroxy-3-nonyl) adenosine hydrochloride (100 micrograms/kg.min, n = 6), an ADA inhibitor, reversed the effect of ADA. Injection of 8-phenyltheophylline (10 mg/kg, n = 6), an adenosine A1 receptor antagonist that alone did not affect GFR, abolished the glycine-induced glomerular hyperfiltration (GFR from 1.02 +/- 0.08 to 0.93 +/- 0.08 ml/min.100 g, P > .05). 8-phenyltheophylline, which itself decreased ERPF, also significantly decreased the ERPF response to glycine (3.47 +/- 0.26 to 2.78 +/- 0.14 ml/min x 100 g). Thus, endogenous adenosine, acting at adenosine A1 receptors, plays an important role in the glomerular hyperfiltration and hyperemia induced by glycine.
Wang
Y X
YX
Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania.
Brooks
D P
DP
D000241:Adenosine / Q000502:physiology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D005998:Glycine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011983:Receptors, Purinergic / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D011983:Receptors, Purinergic; D013806:Theophylline; C028322:8-phenyltheophylline; D000243:Adenosine Deaminase; D000241:Adenosine; D005998:Glycine