title: Biphasic effect of estrogen on neuronal constitutive nitric oxide synthase via Ca(2+)-calmodulin dependent mechanism.
abstract: Estrogen is known to retard the development of atherosclerosis and to work in the brain, but the mechanism of hormonal action is completely unknown. We investigated the effect of estrogen on the activity of neuronal constitutive nitric oxide synthase (NNOS). A low concentration of estrogen (10(-10)(-7) M) enhanced the activity of homogenates of the cytosol fraction of rabbit cerebellums and also that of partially purified NNOS, and high dose (10(-6)(-5) M) attenuated them. The study using estrogen receptor antagonists, tamoxifen, clomiphene, and ICI182780 suggested that estrogen receptor did not relate significantly to those effects of 17 beta-estradiol. 17 alpha-estradiol or progesterone did not change significantly it in low doses, although moderately inhibited it in high doses. Estrogen enhanced the fluorescence of dansyl-calmodulin in low doses and attenuated it in high doses, suggesting that estrogen affects Ca(2+)-calmodulin directly. This study demonstrated that estrogen has a biphasic effect on the activity of NNOS through a Ca(2+)-calmodulin.
authors.affiliation: Department of Geriatrics, Nagoya University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Ishikawa
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: M
authors.initials: M
authors.lastname: Kuzuya
authors.forename: M
authors.initials: M
authors.lastname: Naito
authors.forename: H
authors.initials: H
authors.lastname: Hidaka
authors.forename: A
authors.initials: A
authors.lastname: Iguchi
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002147:Calmodulin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D002531:Cerebellum / Q000201:enzymology*; D002996:Clomiphene / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D000077267:Fulvestrant; D007093:Imidazoles / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D019001:Nitric Oxide Synthase; D011374:Progesterone / Q000494:pharmacology; D011817:Rabbits; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors; D013050:Spectrometry, Fluorescence; D013449:Sulfonamides / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: C035684:5-dimethylaminonaphthalene-1-sulfonyl-calmodulin; D002147:Calmodulin; D007093:Imidazoles; D011960:Receptors, Estrogen; D013449:Sulfonamides; D013629:Tamoxifen; D002996:Clomiphene; D000077267:Fulvestrant; D011374:Progesterone; C031938:calmidazolium; D004958:Estradiol; C017967:W 7; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D002118:Calcium