Regulation of atrial natriuretic peptide receptors in the rat brain.
1. We have studied the localization, kinetics, and regulation of receptors for the circulating form of the atrial natriuretic peptide (ANP; 99-126) in the rat brain. 2. Quantitative autoradiographic techniques and a 125I-labeled ligand, 125I-ANP (99-126), were employed. After in vitro autoradiography, quantification was achieved by computerized microdensitometry followed by comparison with 125I-standards. 3. ANP receptors were discretely localized in the rat brain, with the highest concentrations in circumventricular organs, the choroid plexus, and selected hypothalamic nuclei involved in the production of the antidiuretic hormone vasopressin and in blood-pressure control. 4. Spontaneously (genetic) hypertensive rats showed much lower numbers of ANP receptors than normotensive controls in the subfornical organ, the area postrema, the nucleus of the solitary tract, and the choroid plexus. These changes are in contrast to those observed for receptors of angiotensin II, another circulating peptide with actions opposite to those of ANP. 5. Under conditions of acute dehydration after water deprivation, as well as under conditions of chronic dehydration such as those present in homozygous Brattleboro rats, there was an up-regulation of ANP receptors in the subfornical organ. 6. Our results indicate that in the brain, circumventricular organs contain ANP receptors which could respond to variations in the concentration of circulating ANP. In addition, brain areas inside the blood-brain barrier contain ANP receptors probably related to the endogenous, central ANP system. 7. The localization of ANP receptors and the alterations in their regulation present in genetically hypertensive rats and after dehydration indicate that brain ANP receptors are probably related to fluid regulation, including the secretion of vasopressin, and to cardiovascular function. ANP and angiotensin II could act as mutual antagonists in the brain as they do in the periphery. 8. ANP receptors in the choroid plexus may be related to the formation of cerebrospinal fluid.
Saavedra
J M
JM
Section on Clinical Pharmacology, National Institute of Mental Health, Bethesda, Maryland 20892.
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D051381:Rats; D011910:Rats, Brattleboro; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013045:Species Specificity; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor