Abstract
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.
Footnotes
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Send reprint requests to: Dr. Edwin K. Jackson, Center for Clinical Pharmacology, University of Pittsburgh Medical Center, 623 Scaife Hall, 200 Lothrop Street, Pittsburgh, PA 15213-2582.
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↵1 This work was supported by National Institutes of Health Grants HL55314 and HL35909.
- Abbreviations:
- cAMP
- adenosine-3′-5′-monophosphate
- AMP
- adenosine-5′-monophosphate
- IBMX
- 3-isobutyl-1-methylxanthine
- AMPCP
- α,β-methyleneadenosine-5′-diphosphate
- Received March 18, 1998.
- Accepted July 9, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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