Maturation of A71915-dependent inhibition of atrial natriuretic peptide-stimulated cyclic GMP production in isolated rat glomeruli.
Atrial natriuretic peptide (ANP) regulates glomerular hemodynamics by interaction with biologic receptors (GC-A/ANP) that possess particulate guanylyl cyclase activity. In a previous study we have shown a developmental difference in glomerular response to ANP where preweaned glomeruli produced significantly less extracellular cGMP in response to ANP. Because of the possibility that functional differences in the ANP biologic receptor might exist during development, further characterization of GC-A/ANP receptor response in glomeruli of developing rats was done using a structural analogue of ANP. A71915 (Abbott Laboratories) is a structural analogue of ANP which has been shown to inhibit activation of ANP receptor-associated guanylyl cyclase in vascular smooth muscle cells. The purpose of this study was to investigate the ability of A71915 to inhibit ANP-stimulated cGMP response in isolated glomeruli of adult and preweaned rats. Isolated glomeruli from preweaned or adult rat kidneys were preincubated for 15 min with A71915 (10(-5) M) prior to addition of ANP (up to 10(-6) M). Glomerular response of production of intracellular and extracellular cGMP was measured by radioimmunoassay. Adult glomeruli produced significantly greater amounts of extracellular cGMP compared to preweaned glomeruli for concentrations of ANP > or = 10(-9) M. Infant glomeruli had a significant decrease in the production of ANP-stimulated intracellular cGMP in the presence of A71915 (10(-5) M), whereas extracellular cGMP production was unchanged. In contrast both ANP-stimulated intracellular and extracellular cGMP were significantly decreased by A71915 in adult glomeruli. These results demonstrate the maturation of the glomerular response to ANP.(ABSTRACT TRUNCATED AT 250 WORDS)
Norling
L L
LL
Pediatric Nephrology Unit, Massachusetts General Hospital, Boston 02114.
von Geldern
T
T
Chevalier
R L
RL
D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D006152:Cyclic GMP / Q000096:biosynthesis*; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D044005:Tetrahydroisoquinolines
D010446:Peptide Fragments; D044005:Tetrahydroisoquinolines; C078792:A 71915; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP