Angiotensin II receptor subtypes and angiotensin-converting enzyme in the fetal rat brain.
Angiotensin II (ANG II) receptor subtypes (AT1, displaced by losartan, and AT2, displaced by CGP 42112A) were characterized by quantitative autoradiography after incubation with the ANG II agonist [125I]Sar1-ANG II, in specific brain nuclei of 19-day-old rat embryos. Binding to AT1 receptors, located in the subfornical organ, paraventricular nucleus, nucleus of the solitary tract and choroid plexus, was sensitive to incubation with GTP gamma S. The sensitivity of AT2 receptors to GTP gamma S was heterogeneous. In the ventral thalamic, rostral hypoglossal and medial geniculate nuclei, and in the locus coeruleus, binding to AT2 receptors was sensitive to GTP gamma S and these areas belong to the AT2A subgroup. Conversely, in the inferior olive, medial (fastigial) cerebellar nucleus and caudal part of the hypoglossal nucleus, areas belonging to the AT2B subgroup, binding was insensitive to GTP gamma S. AT2 receptors were also present in cerebral arteries. In the fetal anterior pituitary, AT1 receptors predominated. The angiotensin-converting enzyme (ACE; EC 3.4.15.1) was studied by autoradiography with the selective inhibitor [125I]351A. In 19-day-old embryos, ACE was highly expressed in choroid plexus, with high concentrations in subfornical organ, posterior pituitary and cerebral arteries. No ACE binding was detected in extrapyramidal structures or anterior pituitary in 19-day-old embryos.
Tsutsumi
K
K
Section on Pharmacology, National Institute of Mental Health, Bethesda, MD 20892.
Seltzer
A
A
Saavedra
J M
JM
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000196:embryology* / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D003720:Densitometry; D004151:Dipeptides / Q000494:pharmacology; D005260:Female; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D010902:Pituitary Gland / Q000196:embryology / Q000201:enzymology / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism*
D004151:Dipeptides; D011945:Receptors, Angiotensin; C042037:L-proline, N2-((1S)-1-carboxy-3-phenylpropyl)-N6-((4-hydroxyphenyl)iminomethyl)-L-lysyl-; D000804:Angiotensin II; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D007703:Peptidyl-Dipeptidase A