Physiological Concentrations of Atrial Natriuretic Factors with Intact N-Terminal Sequences Inhibit Corticotropin-Releasing Factor- Stimulated Adrenocorticotropin Secretion from Cultured Anterior Pituitary Cells*

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Abstract
The effectiveness of atrial natriuretic factors (ANFs) as inhibitors of CRF-stimulated ACTH secretion was examined in cultured rat anterior pituitary cells. .alpha.ANF-(1-28) significantly inhibited ACTH release stimulated by 1-5nM CRF. At the most effective concentration of 100 pM, .alpha.ANF-(1-28) inhibited ACTH release by 40.1% (P < 0.001). This effect was manifested after 3 h, but not after 0.5 or 1 h, of incubation, suggesting that ACTH synthesis may have been reduced. Conversely, .alpha.ANF-(5-28), at concentration of 10 pM to 10 nM, had no effect on ACTH secretion after 0.5, 1, or 3 h. .alpha.ANF-(1-11) weakly inhibited ACTH secretion at concentrations of 100 and 1000 pM. Again, these effects were observed after 3h, but not after 0.5 or 1 h, of incubation. These results suggest that ANF-induced inhibition of CRF-stimulated ACTH release requires 1) an intact N-terminal sequence of the ANF peptide, 2) low concentrations, and 3) more than 1 h of incubation. The results explain previous negative evidence and suggest that .alpha.ANF-(1-28) may be a physiological inhibitor of ACTH secretion.