The effects of nephrectomy and probenecid on in vivo clearance of adenosine- 3′,5′-monophosphate from rat plasma

The disappearance of [8-3H]-adenosine 3′,5′-monophosphate (cAMP) from plasma of the intact rat has been investigated. Thirty minutes after the i.v. injection of a pulse of [3H] cAMP with 3 μmole cAMP into 300–400 g rats, more than 99% of the isotope had been removed from the plasma. The disappearance of isotope from the plasma was retarded by probenecid (20–200 mg/kg body weight), bilateral nephrectomy and bilateral nephrectomy plus hepatectomy, in increasing order of their effectiveness. Ligation of both ureters did not alter the rate of isotope disappearance. After the pulse injection, the amount of isotope in the plasma and tissues was determined and the ratio, cpm per g wet tissue/cpm per ml plasma, was calculated. Kidney cortex, kidney inner medulla and liver showed the most striking accumulations of isotope with ratios of 250, 19 and 18, respectively. Probenecid produced a dose-dependent reduction in the accumulation of isotope in kidney cortex and liver. Other tissues which showed some, albeit small, accumulation of isotope were heart (2.0), lung (2.9) and small intestine (1.6). From the accumulation of isotope in the various tissues it was estimated that the kidney cortex accounted for 39%, liver 15%, and urinary excretion 5% of the injected dose of isotope in the untreated rat. It is concluded that in the rat, at least, the kidney cortex is the principal tissue involved in cAMP removal (and degradation) from the plasma.