Interaction of natriuretic peptides and cGMP production via the same receptor in mouse astrocytes

Atrial and brain natriuretic peptides have been found previously to bind to specific receptors on cultured mouse astrocytes and to stimulate cyclic guanosine 5-monophosphate (cGMP) production with similar dose dependency although brain natriuretic peptide (BNP) shows a greater maximal stimulatory effect. The present study provides evidence that both peptides work through the same pathway. No additive or synergistic effect was observed when astrocytes were exposed to both peptides. However, human ANF(99-126) at high concentrations partially inhibited porcine BNP induced cGMP production to the level seen with ANF alone. ANF could be viewed as a partial agonist of pBNP competing for the same effector sites. Differences in structure between human ANF(99-126) and porcine BNP may account for the difference in cGMP response. The interaction between the two peptides and the cGMP response does not reflect receptor binding affinities and is likely to be a post-binding event.