TY - JOUR T1 - Evidence for an Endogenous cAMP-Adenosine Pathway in the Rat Kidney JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 926 LP - 930 VL - 287 IS - 3 AU - Zaichuan Mi AU - Edwin K. Jackson Y1 - 1998/12/01 UR - http://jpet.aspetjournals.org/content/287/3/926.abstract N2 - In the rat kidney, exogenous adenosine-3′-5′-monophosphate (cAMP) is converted to adenosine via the metabolism of cAMP to adenosine-5′-monophosphate by phosphodiesterase and adenosine-5′-monophosphate to adenosine by 5′-nucleotidase. Our purpose was to investigate whether in the rat kidney adenosine is synthesized from endogenous cAMP via the same pathway. Rat kidneys were perfused with Tyrode’s solution, and stabilized for 3 hr to minimize basal renal purine secretion. In control experiments (n = 6), the renal venous secretion rate of adenosine, inosine, hypoxanthine and Σpurines (adenosine + inosine + hypoxanthine) did not change over the two 10-min experimental periods. In contrast, thebeta adrenoceptor agonist (±)-isoproterenol (1 and 10 μM added to the perfusate) caused a significant (1-factor analysis of variance with repeated measures; n = 31) increase in the renal venous secretion of adenosine (P < .0001), inosine (P < .0007), hypoxanthine (P < .0007) and Σpurines (P < .0001) as measured by high-performance liquid chromatography with ultraviolet detection. The Σpurines was the most discriminating index of isoproterenol-induced changes in purine release, and the renal venous secretion of Σpurines was significantly (2-factor analysis of variance with repeated measures) attenuated by inhibition ofbeta adrenoceptors with propranolol (.1 μM,n = 6; P < .05), phosphodiesterase with 3-isobutyl-1-methylxanthine (1 mM, n = 5; P < .002) and 5′-nucleotidase with α,β-methyleneadenosine-5′-diphosphate (0.1 mM, n = 5; P < .03). Our data indicate that activation of betaadrenoceptors increases purine biosynthesis in the rat kidney via a mechanism that involves phosphodiesterase and 5′-nucleotidase. These results support the existence of an endogenous cAMP-adenosine pathway in the rat kidney. The American Society for Pharmacology and Experimental Therapeutics ER -