Angiotensin-II receptor subtypes in median eminence and basal forebrain areas involved in regulation of pituitary function.
We used quantitative autoradiography to characterize angiotensin-II (ANG-II) receptor subtypes in areas of the rat basal forebrain involved in pituitary control. ANG binding was totally displaced by the selective AT1 receptor subtype antagonist DuP 753 and was inhibited by dithiothreitol in median eminence, infundibular stem, paraventricular nucleus, subfornical organ, median preoptic nucleus, anterior pituitary, and the forebrain ANG-II receptor band, which extends from the subfornical organ to the vascular organ of the lamina terminalis, including the lamina terminalis and a continuous band of receptors reaching the paraventricular nucleus. In these areas, binding was not affected by the selective AT2 competitors PD 123177 or CGP 42112 A, indicating the presence of AT1 and the absence of AT2 receptors. AT1 binding was higher in the external layer and lateral parts of the median eminence. Conversely, ANG binding in the dura mater encapsulating the pituitary, in the vessels adjacent to this part of the dura mater, presumably branches of the hypophyseal arteries, and in anterior cerebral arteries was displaced by PD 123177 and CGP 42112 A, and was unaffected by dithiothreitol or DuP 753, indicating the presence of AT2 receptors in these structures. Our results implicate AT1 receptors in the central neural regulation of pituitary function. AT2 receptors may play a role in the regulation of blood flow to the basal forebrain and the pituitary gland.
Tsutsumi
K
K
Section on Pharmacology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892.
Saavedra
J M
JM
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001713:Biphenyl Compounds / Q000378:metabolism; D002536:Cerebral Arteries / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology; D019808:Losartan; D008297:Male; D008473:Median Eminence / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology; D010902:Pituitary Gland / Q000098:blood supply / Q000502:physiology*; D016548:Prosencephalon / Q000098:blood supply / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000378:metabolism*; D013777:Tetrazoles / Q000378:metabolism
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D009842:Oligopeptides; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C066253:PD 123177; C060894:CGP 42112A; D019808:Losartan; D004229:Dithiothreitol