Identification and quantification of 2',3'-cAMP release by the kidney.
J Pharmacol Exp Ther
; 328(3): 855-65, 2009 Mar.
Article
em En
| MEDLINE
| ID: mdl-19033554
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nucleotídeos de Adenina
/
Hipertensão
/
Rim
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Pharmacol Exp Ther
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos