AJP - Regulatory, Integrative and Comparative Physiology, Vol 264, Issue 3 513-R523, Copyright © 1993 by American Physiological Society
C-type natriuretic peptide and atrial natriuretic peptide receptors of rat brain
J. Brown and Z. Zuo
Physiological Laboratory, Cambridge, United Kingdom.
Natriuretic peptide receptors in rat brain were mapped by in vitro
autoradiography using 125I-labeled [Tyr0]CNP-(1-22) to bind atrial
natriuretic peptide receptor (ANPR)-B and ANPR-C receptors selectively, and
125I-labeled alpha-ANP to select ANPR-A and ANPR-C receptors.
Des-[Gln18,Ser19,Gly20,Leu21,Gly22]ANP-(4- 23)-amide (C-ANP) was used for
its selectivity for ANPR-C over ANPR-A. Specific binding of
125I-[Tyr0]CNP-(1-22) with a dissociation constant (Kd) approximately 1 nM
occurred in olfactory bulb, cerebral cortex, lateral septal nucleus,
choroid plexus, and arachnoid mater. This binding was abolished by C-type
natriuretic peptide [CNP-(1-22)], alpha-ANP and C-ANP, and conformed to
ANPR-C. 125I-alpha-ANP bound to all structures that bound
125I-[Tyr0]CNP-(1-22). This binding was also inhibited by both CNP-(1-22)
and C-ANP, confirming the presence of ANPR-C-like binding sites. However,
ANPR-C-like binding sites were heterogenous because only some had high
affinities for 125I-[Tyr0]CNP-(1-22) and CNP-(1-22). 125I-alpha-ANP also
bound sites without affinities for C-ANP or CNP-(1-22). These sites were
consistent with ANPR-A. They occurred mainly on the olfactory bulb, the
choroid plexus, and the subfornical organ. Guanosine 3',5'-cyclic
monophosphate production was strongly stimulated by alpha-ANP but not by
CNP-(1-22) in olfactory bulb. Neither ligand stimulated it in cortical
tissue. Thus the natriuretic peptide binding sites of rat brain conformed
to ANPR-A and to heterogenous ANPR-C-like sites. No ANPR-B were detected.
