LOCALIZATION OF NATRIURETIC PEPTIDE-ACTIVATED GUANYLATE-CYCLASE MESSENGER-RNAS IN THE RAT-BRAIN

Physiological actions of atrial natriuretic peptide (ANP) and C-type n atriuretic peptide (CNP) are elaborated by membrane-bound natriuretic peptide receptors (NPRs). These receptors possess intracellular guanyl ate cyclase domains that mobilize cyclic guanosine monophosphate upon binding of peptide. Two distinct NPR subtypes have been described in b rain: the NPR-A selectively binds ANP, whereas NPR-B exhibits high aff inity for CNP. To define further the potential domains of ANP and CNP action in brain, the present study used in situ hybridization histoche mistry to map NPR-A and NPR-B mRNA-expressing cell populations. Signif icant levels of neuronal NPR-A mRNA expression were observed only in t he mitral cell layer of the olfactory bulb, medial habenula, subfornic al organ, and area postrema. Expression of NPR-A mRNA was observed in forebrain white matter tracts, suggesting synthesis in glial cells. In contrast, NPR-B mRNA was widely expressed throughout the neuraxis. In the telencephalon, signal was abundant throughout limbic cortex and n eocortex, olfactory bulb, hippocampus, and amygdala. Intense NPR-B mRN A hybridization was observed in preoptic-hypothalamic neuroendocrine c ircuits and in motor nuclei of cranial nerves. Intermediate expression of NPR-B mRNA was observed in brainstem nuclei controlling autonomic function. Labeling for NPR-B but not NPR-A mRNA was observed in pituic ytes in the neural lobe of the pituitary and in scattered cells of the anterior pituitary. These results suggest that CNP is the primary bio logically active natriuretic peptide in brain. In contrast with NPR-B, NPR-A appears to be expressed largely in restricted cell populations containing high levels of ANP and in circumventricular organs. These d ata implicate the NPR-A in autoregulation of ANP neurons and central r egistration of cardiac ANP release. (C) 1996 Wiley-Liss, Inc.