title: Modulation of angiotensin II binding sites in neuronal cultures by mineralocorticoids.
abstract: Previous studies have determined that mineralocorticoid hormones are able to increase the number of angiotensin II (ANG II)-specific binding sites in rat diencephalon and in neuronal cultures and also increase the drinking response elicited by centrally injected ANG II. In the present study, we have examined the specificity and mechanisms of this mineralocorticoid action. In neuronal cultures from the hypothalamus and brain stem (H/BS), both D-aldosterone and deoxycorticosterone acetate (DOCA) caused significant time- and dose-dependent increases in 125I-labeled ANG II-specific binding. This effect was not mimicked by the synthetic glucocorticoid dexamethasone, or by testosterone, beta-estradiol or progesterone. However, the steroid corticosterone induced a moderate increase in [125I] ANG II binding. This may have occurred as a result of its high affinity for the mineralocorticoid type I receptor. DOCA was ineffective in increasing [125I]ANG II specific binding both in neuronal cultures prepared from the cerebellum and in pure astrocytic glial cultures, indicating that this mineralocorticoid effect is specific both for neurons and for certain brain regions. The increase in [125I]ANG II-specific binding elicited by DOCA was abolished by cotreatment with the mineralocorticoid receptor blockers mespirenone or ZK97894 and by cotreatment with cycloheximide. Taken together, these observations suggest that the mineralocorticoid-induced increase in [125I]ANG II-specific binding in H/BS neuronal cultures is a specific event, which is mediated via mineralocorticoid type I receptors and which requires protein synthesis.
authors.affiliation: Department of Physiology, College of Medicine, University of Florida, Gainesville 32610.
authors.forename: C
authors.initials: C
authors.lastname: Sumners
authors.forename: M J
authors.initials: MJ
authors.lastname: Fregly
mesh_terms: D000450:Aldosterone / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001933:Brain Stem / Q000378:metabolism*; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism*; D008901:Mineralocorticoids / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology
chemical_list: D008901:Mineralocorticoids; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D013148:Spironolactone; D013739:Testosterone; D003900:Desoxycorticosterone; D000450:Aldosterone; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone; C058243:ZK 97894; D003513:Cycloheximide; C051308:mespirenone; D003345:Corticosterone