Generation of cyclic guanosine monophosphate in brain slices incubated with atrial or C-type natriuretic peptides: comparison of the amplitudes and cellular distribution of the responses

Abstract

Natriuretic peptides have been demonstrated to induce a variety of effects when administered into the brain. Most studies to date have tested the effects of ‘atrial’ natriuretic peptide (ANP), but C-type natriuretic peptide (CNP) has recently been suggested to be the predominant form of natriuretic peptides within the brain. We therefore have compared the amplitudes of the cyclic guanosine monophosphate (cGMP) responses induced by either ANP or CNP in slices from different rat brain regions. Whereas both peptides induced the generation of cGMP, CNP-evoked responses were never greater than those obtained with ANP, regardless of the brain region used or the age of the animal. In diencephalon, ANP even induced a significantly higher cGMP response than CNP. To test which cells were targets to the actions of the peptides, brain slices were incubated with fluorocitrate (a drug that selectively blocks the metabolism of glial cells). Fluorocitrate totally blocked the ANP-evoked cGMP responses in brain slices. In contrast, fluorocitrate reduced only partially the responses evoked by sodium nitroprusside (a drug that stimulates soluble guanylate cyclase, which is contained predominantly in neurons). Likewise, the cGMP response induced by CNP was only partially affected by fluorocitrate. These results indicate that: (1) CNP is not more potent than ANP in terms of its ability to generate cGMP in rat brains; (2) brain cells generating cGMP upon exposure to ANP are predominantly glial; and (3) CNP-responsive cells are partly glial, but belong at least in part to a different compartment than ANP-responsive cells. All together, these data suggest that there is a functional separation between the effects of ANP and CNP in rat brains.