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Identification and quantification of 2',3'-cAMP release by the kidney.

Abstract
We recently developed a sensitive assay for 3',5'-cAMP using high-performance liquid chromatography-tandem mass spectrometry. Using this assay, we investigated the release of 3',5'-cAMP from isolated, perfused rat kidneys. To our surprise, we observed a dominant chromatographic peak that was because of an endogenous substance that had the same parent ion as 3',5'-cAMP and that fragmented to the same daughter ion (adenine) as 3',5'-cAMP. However, the retention time of this unknown was approximately 2.9 min, compared with 6.3 min for authentic 3',5'-cAMP. We hypothesized that the unknown substance was an isomer of 3',5'-cAMP. The unknown substance had the same retention time and mass spectral properties as authentic 2',3'-cAMP. Renal venous secretion of 2',3'-cAMP was greater in kidneys from 20-week-old genetically hypertensive rats compared with age-matched normotensive rats (12.49 +/- 2.14 versus 5.32 +/- 1.97 ng/min/g kidney weight, respectively; n = 18). Isoproterenol (1 microM; beta-adrenoceptor agonist) increased renal venous 3',5'-cAMP secretion (approximately 690% of control) but had no effect on 2',3'-cAMP production. In contrast, rapamycin (0.2 microM; activator of mRNA turnover) and iodoacetate + 2,4-dinitrophenol (50 microM; metabolic inhibitors) increased the renal venous secretion of 2',3'-cAMP (approximately 1000 and 4100% of control, respectively) while simultaneously decreasing the renal venous secretion of 3',5'-cAMP. In conclusion, 2',3'-cAMP is a naturally occurring isomer of 3',5'-cAMP that is: 1) not made by adenylyl cyclase; 2) released from kidneys into the extracellular compartment; 3) released more by kidneys from rats with long-standing hypertension; 4) derived from mRNA turnover; and 5) increased by energy depletion.
AuthorsJin Ren, Zaichuan Mi, Nicolas A Stewart, Edwin K Jackson
JournalThe Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 328 Issue 3 Pg. 855-65 (Mar 2009) ISSN: 1521-0103 [Electronic] United States
PMID19033554 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Adenine Nucleotides
  • 2',3'-cyclic AMP
  • Cyclic AMP
Topics
  • Adenine Nucleotides (chemistry, metabolism)
  • Animals
  • Chromatography, High Pressure Liquid
  • Cyclic AMP (analysis)
  • Hypertension (metabolism)
  • Kidney (metabolism)
  • Male
  • Mass Spectrometry
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY

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