Receptor subtypes for natriuretic peptides in the brains of hypertensive rats

Receptor subtypes for alpha-atrial natriuretic peptide (alpha-ANP) were characterized in brains of 12-wk-old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) by in vitro autoradiography, using des[Gln18, Ser19,Gly20,Leu21,Gly22]ANP-(4-23) (C-ANP) and ANP-(5-25) as subtype-selective ligands. 125I-labeled alpha-ANP (200 pM) bound reversibly to arachnoid mater (AM), choroid plexus (ChP), subfornical organ (SFO), median preoptic nucleus, and supraoptic nucleus. Apparent Kd values for alpha-ANP in AM, ChP, and SFO were 1-6 nM and they were lowest in SHR. Maximal binding capacities for alpha-ANP on ChP and SFO were also significantly lower in SHR, and 10 microM C-ANP or 10 microM ANP-(5-25) inhibited most radioligand binding on AM of WKY and SHR. C-ANP significantly inhibited no other alpha-125I-ANP binding. ANP-(5-25) was a relatively weak inhibitor of alpha-125I-ANP binding to ChP and SFO in WKY but it was powerful in SHR. The results suggest that AM expresses clearance receptor for alpha-ANP in WKY and SHR. Other structures do not express this receptor significantly but express two other receptors for alpha-ANP, one mainly in WKY and one mainly in SHR.