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

J Pharmacol Exp Ther. 1986 Nov;239(2):474-9.

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 (T1/2 = 31 sec) and nephrectomized (T1/2 = 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.

MeSH terms

  • Animals
  • Atrial Natriuretic Factor / blood
  • Atrial Natriuretic Factor / metabolism*
  • Deamino Arginine Vasopressin / analogs & derivatives
  • Deamino Arginine Vasopressin / pharmacology
  • Half-Life
  • Heart Atria / metabolism
  • Kinetics
  • Male
  • Myocardium / metabolism*
  • Nephrectomy
  • Peptide Fragments / blood
  • Rats
  • Rats, Inbred Strains
  • Time Factors

Substances

  • Peptide Fragments
  • vasopressin, deamino-homo-Arg-
  • Atrial Natriuretic Factor
  • Deamino Arginine Vasopressin