Atrial natriuretic factor (ANF) has been suggested to exert a tubular effect on the mammalian nephron, perhaps in part by interacting with other hormones. In the present study, the effect of ANF was examined on glomeruli (Gm) and different renal tubule segments including medullary (MAL) and cortical thick ascending limb (CAL) and cortical (CCT), outer medullary (OMCT) and inner medullary collecting tubules (IMCT). This effect of ANF was assessed by alteration in adenylate cyclase and cGMP in the various nephron segments in the presence and absence of arginine vasopressin (AVP), parathyroid hormone (PTH) and calcitonin (SCT). An effect of ANF (10(-8) M) was not demonstrated on adenylate cyclase (fmol cAMP formed/30 min/micrograms protein) in Gm, CAL, MAL, CCT, OMCT or IMCT. Nor did ANF (10(-8) M) interfere with the effect of PTH (5 IU/ml) on the Gm (PTH 35.1 +/- 3.7 vs. PTH + ANF 32.5 +/- 1.8, NS), CAL (PTH 50.5 +/- 10.9 vs. PTH + ANF 46.2 +/- 1.4, NS) or AVP (10(-8) M) on the CCT (AVP 40.8 +/- 6.6 vs. AVP + ANF 33.0 +/- 3.1, NS), OMCT (AVP 56.0 +/- 11.8 vs. AVP + ANF 42.1 +/- 6.7, NS), IMCT (AVP 66.5 +/- 4.6 vs. AVP + ANF 53.5 +/- 7.0, NS) or MAL (AVP 15.5 +/- 1.6 vs. AVP + ANF 14.0 +/- 2.6, NS). ANF also did not affect SCT (1.5 x 10(-8) M)-induced adenylate cyclase on CCT (SCT 69.8 +/- 11.3 vs. SCT + ANF 79.9 +/- 7.2, NS). ANF (10(-8) M), however, significantly increased cGMP in the Gm (6.4 +/- 1.7 to 121.3 +/- 32.4 fmol/micrograms protein, P less than 0.001) and IMCT (0.63 +/- 0.16 to 1.46 +/- 0.29 fmol/micrograms protein, P less than 0.05). However, no effect of ANF on cGMP was observed in the CAL, CCT, OMCT, and MAL even at 10(-7) M ANF. PTH (5 IU/ml) did not alter either basal or ANF-stimulated cGMP in the Gm. Also, specific ANF binding was studied in the microdissected IMCT. Kd was 6.08 x 10(-9) M and Bmax was 8.07 x 10(-11) M.(ABSTRACT TRUNCATED AT 250 WORDS)