EXPRESSION AND GLUCOCORTICOID REGULATION OF NATRIURETIC PEPTIDE CLEARANCE RECEPTOR (NPR-C) MESSENGER-RNA IN RAT-BRAIN AND CHOROID-PLEXUS

The natriuretic peptide clearance receptor (NPR-C) binds atrial natriu retic peptide, brain natriuretic peptide and C-type natriuretic peptid e with high affinity. This receptor lacks an intracellular guanylate c yclase domain, and is believed to exert biological actions by sequestr ation of released natriuretic peptides and/or inhibition of adenylate cyclase. The present report summarizes the first detailed mapping of N PR-C mRNA in rat brain. In situ hybridization analysis revealed high l evels of NPR-C mRNA expression in frontal and retrosplenial granular c ortices, medial preoptic nucleus, ventral cochlear nucleus and choroid plexus. NPR-C mRNA expression was also observed in deep layers of neo cortex and limbic cortex, posterior cortical amygdala, ventral subicul um, amygdalohippocampal area, and dentate gyrus. Positive hybridizatio n signal was observed in both anterior and intermediate lobes of the p ituitary gland. Regulatory studies indicated that expression of NPR-C mRNA was increased in the medial preoptic nucleus of adrenalectomized rats, suggesting negative glucocorticoid regulation. No changes in NPR -C mRNA expression were observed in frontal cortex or choroid plexus. These results suggest a role for the NPR-C in modulation of natriureti c peptide availability and/or adenylate cyclase activity in a subset o f central natriuretic peptide circuits concerned with cortical, olfact ory and neuroendocrine functions. Response of the NPR-C gene to change s in circulating hormones suggests the capacity for glucocorticoid mod ulation of natriuretic peptide action at the receptor level.