Atriopeptins are potent inhibitors of ACTH secretion by rat anterior pituitary cells in vitro: involvement of the atrial natriuretic factor receptor domain of membrane-bound guanylyl cyclase.

The current concept of the regulation of adenohypophysial corticotrophin secretion assigns a stimulatory role to neuropeptides of hypothalamic origin and an inhibitory function to adrenocortical glucocorticoid hormones. It has been shown that in isolated perifused rat anterior pituitary cells atriopeptins (1-28) and (5-28), but not (5-25), potently suppress corticotrophin secretion elicited by 41-residue corticotrophin-releasing factor and arginine vasopressin. The action of atriopeptins is associated with a marked increase in the cellular content of cyclic GMP. Moreover, 8-Br-cyclic GMP, a cell membrane permeant analogue of cyclic GMP, also inhibited secretagogue-stimulated corticotrophin release. It is suggested that atrio-peptins of hypothalamic and perhaps of cardiac origin may be functionally significant corticotrophin-release inhibiting factors.