Effect of atrial natriuretic factor (ANF)-related peptides on aldosterone secretion by adrenal glomerulosa cells: critical role of the intramolecular disulphide bond.

We previously demonstrated that synthetic 48-73 atrial natriuretic factor (ANF) (previously called 8-33 ANF) blocked the response of rat adrenal glomerulosa cells to angiotensin II, ACTH and potassium. We have now investigated the effects of natural 43-73 ANF, oxidised synthetic 48-73 ANF and the natural 1-73 ANF on aldosterone output by rat glomerulosa cells. The natural 43-73 ANF and the natural 1-73 ANF were equipotent to 48-73 ANF in inhibiting the stimulation of aldosterone secretion produced by angiotensin II with an IC50 of 2 X 10(-9)M. Similar results were obtained with ACTH and potassium. After oxidation with performic acid, 48-73 ANF was completely devoid of activity on the response of aldosterone to angiotensin II, ACTH and potassium. We conclude that the intramolecular disulphide bond in 48-73 ANF is critical for maintaining the active conformation of ANF.