Effect of atrial natriuretic factor on adenylate cyclase in various nephron segments

Abstract

The effects of rat synthetic atrial natriuretic factor (ANF) [Arg101, Tyr126] were studied on adenylate cyclase activity in various renal structures such as glomeruli, proximal tubules, loops of Henle, and collecting ducts from dog kidney. ANF inhibited adenylate cyclase activity in glomeruli, loops of Henle, and collecting ducts, but not in proximal tubules, in a concentration-dependent manner. The maximal inhibitions observed were approximately 45% in glomeruli and collecting ducts with an apparent Ki of 10(-10)-10(-9) M and 30% in loops of Henle with an apparent Ki of 10(-11)-5 X 10(-10) M. ANF also inhibited the stimulatory responses of various hormones and forskolin on adenylate cyclase in glomeruli, collecting ducts, and loops of Henle. However, the extent of inhibition varied in the three fractions. In addition, ANF showed an additive effect with the inhibitory response of angiotensin II on adenylate cyclase in glomeruli. These data indicate that ANF receptors coupled to adenylate cyclase are present in glomeruli, loops of Henle, and collecting ducts and not in proximal tubules, and it can be suggested that the inhibition of adenylate cyclase by ANF may be one of the mechanisms through which ANF regulates kidney functions.