AJP - Renal Physiology, Vol 250, Issue 1 27-F31, Copyright © 1986 by American Physiological Society
Atriopeptin III increases cGMP in glomeruli but not in proximal tubules of dog kidney
T. J. Stokes Jr, C. L. McConkey Jr and K. J. Martin
Atriopeptin III is natriuretic, diuretic, and phosphaturic in the intact
dog and relaxes vascular and nonvascular smooth muscle in vitro. The
mechanism of the renal effects of atriopeptin remains ill defined but may
include hemodynamic alterations and/or direct tubular effects. Since many
peptide hormones act through changes in cyclic nucleotide formation, we
examined the effect of synthetic atriopeptins on cAMP and cGMP accumulation
in isolated glomeruli and proximal tubules from normal dog kidney.
Synthetic atriopeptin produced a dose-related increase in cGMP in glomeruli
with a Kact of 200 +/- 19 nM and a maximal activity of 64.1 +/- 6.3 pmol
cGMP X mg prot-1 X 5 min-1. In the presence of 4 mM Mn2+ Kact was reduced
to 19 +/- 2 nM with no change in maximal cGMP production (66.2 +/- 11.8
pmol cGMP X mg prot-1 X 5 min-1). Atriopeptin (1 microM) did not increase
cGMP accumulation above basal levels in proximal tubule segments. The cAMP
production of neither glomeruli nor proximal tubules was stimulated by
atriopeptin. These studies demonstrate a dose-dependent stimulation of
guanylate cyclase by atriopeptin in glomeruli but not in proximal tubule
segments. In addition, atriopeptin neither stimulates nor inhibits cAMP
accumulation in glomeruli or proximal tubules. These data suggest a major
role for the renal effects of atriopeptin at the glomerular level, possibly
through hemodynamic effects or changes in the glomerular ultrafiltration
coefficient.(ABSTRACT TRUNCATED AT 250 WORDS)
