Characterisation of the effects of natriuretic peptides upon ACTH secretion from the mouse pituitary

The involvement of natriuretic peptides in the regulation of ACTH secretion in mice hemi-pituitary preparations was investigated. Atrial natriuretic p eptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptid e (CNP) all inhibited CRF (10(-9) M)-evoked ACTH secretion over a concentra tion range of 10(-12)-10(-10) M and also stimulated cyclic GMP accumulation over a concentration range of 10(-8)-10(-5) M. CNP was the most effective both in the inhibition of ACTH secretion and in the stimulation of cyclic G MP accumulation. Coincubation of hemi-pituitaries with 8bromo-cyclic GMP (1 0(-4) M) completely inhibited CRF (10(-9) M)-evoked ACTH secretion. Norther n blot analysis revealed that all three major isoforms of the natriuretic p eptide receptors are expressed in the mouse pituitary. These results demons trate that natriuretic peptides do inhibit CRF-stimulated ACTH secretion fr om mouse pituitary preparations. A role for cGMP in mediating this effect o n hormone secretion is indicated but the discrepancy between the efficacies of natriuretic peptides in inhibiting the secretory response and stimulati ng cyclic GMP accumulation suggest a more complicated stimulus-secretion co upling pathway is in operation. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.