Natriuretic peptide receptors are expressed during cerebral growth
in the fetal rat.
Brown, J., and Z. Zuo.
Physiological Laboratory, University of Cambridge, Downing Street,
Cambridge CB2 3EG.
APStracts 2:0036E, 1995.
Autoradiography of frozen sections of fetal rat brain shows that
receptor-like binding sites for atrial and C-type natriuretic
peptides (ANP and CNP) occur in the generative juxtaventricular zone
of the telencephalon after the twelfth embryonic day (E12). These
sites avidly bind both ANP and CNP. They thus resemble the cloned
NPR-C natriuretic peptide receptor. Covalent cross-linking of 125I
-tyro-CNP(1-22) and 125I-ANP(1-28) to membrane proteins from E16
telencephala labels a single protein band on reducing sodium dodecyl
sulphate (SDS)-polyacrylamide gel electrophoresis. The protein has
high affinities for ANP and CNP, and a molecular mass of 60-70 kDa
under reducing conditions, consistent with reduced NPR-C. However,
the telencephalic protein has unusual physico-chemical properties in
SDS under non-reducing conditions so it was not possible to assess
whether this protein can form disulphide-bridged dimers like NPR-C.
CNP(1-22) was a full agonist, and ANP(1-28) was a partial agonist of
guanosine 3',5'-cyclic monophosphate (cGMP) production by E16
telencephalon. C-ANP, a synthetic ligand of NPR-C, antagonised CNP(1
-22)-mediated cGMP production. The results imply either that the NPR
-C-like telencephalic receptor modulates the level of cGMP or that a
guanylate cyclase-coupled receptor such as the 120 kDa NPR-B, for
which CNP(1-22) is a full agonist, is present at levels insufficient
to be detected by autoradiography or protein labelling. Our findings
demonstrate that natriuretic peptide receptors occur in the fetal
telencephalon when future cortical neurones are being born.
Consequently, natriuretic peptides may be growth modulators in
embryonic cerebral cortex.
Received 16 November 1994; accepted in final form 13 February
1995.
APS Manuscript Number E473-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 1 March 1995.