Atriopeptin turnover: Quantitative relationship between in vivo changes in plasma levels and atrial content

N. Katsube, D. Schwartz, P. Needleman

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Administration of the 1-deamino-arginine8 vasopressin caused a decrease in right, but not left, atrial levels of atriopeptin (AP) in chloral hydrate-anesthetized rats. The amount of exogenous AP required to match the 1-deamino-arginine8 vasopressin-stimulated plasma levels of AP was equivalent to the decrease in AP content of the right atrium, suggesting that resynthesis of AP did not occur within the 60 min after 1-deamino-arginine8 vasopressin stimulation. The correlation between increased plasma levels and decreased atrial content was also observed in bilaterally nephrectomized rats, suggesting that the kidney is not a major site of degradation of AP in vivo. This finding was confirmed by the comparison of the half-life of exogenous AP in normal (T( 1/2 ) = 31 sec) and nephrectomized (T( 1/2 ) = 64 sec) animals. Plasma immunoreactivity of the N-terminal fragment of the prohormone (which is also released after cleavage of the precursor peptide) increased 35-fold by 24 hr after nephrectomy in comparison with a 5-fold increase in AP. Half-life studies of the N-terminal fragment suggest that the kidney is the major site of degradation of this molecule. This study demonstrated the different kinetics and renal metabolism of the AP and N-terminal portions of the prohormone.

Original languageEnglish
Pages (from-to)474-479
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume239
Issue number2
StatePublished - Dec 1 1986

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