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 peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) all inhibited CRF (10(-9) M)-evoked ACTH secretion over a concentration 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 GMP accumulation. Coincubation of hemi-pituitaries with 8bromo-cyclic GMP (10(-4) M) completely inhibited CRF (10(-9) M)-evoked ACTH secretion. Northern blot analysis revealed that all three major isoforms of the natriuretic peptide receptors are expressed in the mouse pituitary. These results demonstrate that natriuretic peptides do inhibit CRF-stimulated ACTH secretion from mouse pituitary preparations. A role for cGMP in mediating this effect on hormone secretion is indicated but the discrepancy between the efficacies of natriuretic peptides in inhibiting the secretory response and stimulating cyclic GMP accumulation suggest a more complicated stimulus-secretion coupling pathway is in operation.