Korean J Physiol Pharmacol.  1997 Jun;1(3):325-335.

Renal effects of chronic treatment of adenosine analogues

• Kim TH
• Kim SH
• Huh J
• Cho KW

Abstract

Evidence for the existence of at least two subclasses of renal adenosine receptors has been presented. N-6-cyclohexyladenosine (CHA) is a relatively selective A-1 adenosine agonists, whereas 5'-N-ethylcarboxamidoadenosine (NECA) acts as a preferential agonist of A-2 adenosine receptor. N6-(L-2-phenylisopropyl)-adenosine (PIA) almost unselectively activates both A-1 and A-2 adenosine receptors at micromolar concentrations. During the characterization of adenosine receptor in the kidney, we have discovered a novel phenomenon, that is, an intramuscular administration of CHA for 3 days caused a diuresis and a suppression of urinary concentrating ability. To further characterize this novel phenomenon, an intramuscular administration of adenosine and other adenosine angonists, PIA and NECA, and prior treatment of adenosine antagonists, caffeine, theophylline and 1,3-diethyl-8-phenyl-xanthine (DPX) were performed. Systemic administration of CHA, PIA, and NECA for 3 days caused a suppression in heart rate, blood pressure and general motor activity without change in rectal temperature. Systemic administration of CHA, 0.5, 1 and 2 mg/kg/day, for 3 days caused a dose-dependent increase in urine volume and decrease in urinary osmolarity and free water reabsorption. This phenomenon was reversible and repeatable. Administration of adenosine (40 mg/kg/day) produced no apparent effect on the renal function, whereas PIA (2 mg/kg/day) produced an similar effect to CHA on the renal function. Systemic administration of NECA, 0.025, 0.05 and 0.25 mg/kg/day, for 3 days caused a dose-dependent increase in urine volume and dose-dependent increases in excreted amount of creatinine, urinary osmolarity and free water reabsorption. These renal effects of adenosine agonist were maximum at second day during the drug administration. In terms of increase in urine volume and the suppression of urinary concentrating ability, NECA was potent than CHA. Prior treatment of caffeine (50 mg/kg/day) or theophylline (50 mg/kg/day) abolished the diuretic effect of, CHA, whereas DPX (50 mg/kg/day) did not affect the CHA effect. CHA, 0.5 mg/kg/day, produced no change in plasma renin activity and plasma levels of aldosterone, epinephrine, and norepinephrine. These results suggest that this novel phenomenon produced by an activation of renal adenosine receptors plays an important role in urinary concentrating mechanism.

MeSH Terms

Adenosine*
Adenosine-5'-(N-ethylcarboxamide)
Aldosterone
Blood Pressure
Caffeine
Creatinine
Diuresis
Diuretics
Epinephrine
Heart Rate
Kidney
Motor Activity
Norepinephrine
Osmolar Concentration
Plasma
Receptors, Purinergic P1
Renin
Theophylline
Water
Adenosine
Adenosine-5'-(N-ethylcarboxamide)
Aldosterone
Caffeine
Creatinine
Diuretics
Epinephrine
Norepinephrine
Receptors, Purinergic P1
Renin
Theophylline
Water