title: Estrogens act in rat hippocampus and frontal cortex to produce rapid, receptor-mediated decreases in serotonin 5-HT(1A) receptor function.
abstract: Previously our laboratory has shown that 17beta-estradiol in vivo rapidly decreases R(+)-8-OH-DPAT-stimulated [(35)S]GTPgammaS binding (a measure of the initial biochemical event in the intracellular signaling pathway associated with 5-HT(1A) receptors) in the hippocampus, frontal cortex and amygdala. Studies were designed to determine if 17beta-estradiol also acts in vitro on estrogen receptors in the hippocampus and frontal cortex to decrease 5-HT(1A) receptor function. Hippocampus and frontal cortex were dissected from ovariectomized rats and incubated for up to 3 h with various estrogens and antiestrogens; membrane homogenates were prepared for R(+)-8-OH-DPAT-stimulated [(35)S]GTPgammaS binding assays. 17beta-Estradiol (10(-6) M) decreased the maximal response in the R(+)-8-OH-DPAT-stimulated [(35)S]GTPgammaS binding assay in a time-dependent manner (observed at 30, 60 and 120 min) in both hippocampus and frontal cortex. The hormone, however, did not alter the EC(50) of R(+)-8-OH-DPAT. When hippocampus and frontal cortex were incubated in graded concentrations of 17beta-estradiol for 1 h, the calculated EC(50) was approximately 2.5 x 10(-8) M in both brain regions. The nonestradiol estrogen diethylstilbestrol also decreased 5-HT(1A) receptor function while the less potent estrogens 17alpha-estradiol and estriol were inactive at 5 x 10(-8) M. The estrogen receptor antagonist ICI 182,780 potently and completely blocked the effects of 17beta-estradiol on 5-HT(1A) receptor function with an apparent K(B) of approximately 10(-9) M. These data demonstrate clearly that estrogens can act on estrogen receptors located in hippocampus and frontal cortex of ovariectomized rats to produce rapid heterologous decreases in 5-HT(1A) receptor function.
authors: Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas School of Medicine, 3901 Rainbow Blvd., Kansas City, KS 66160-7417, USA.
authors: A L
authors: AL
authors: Mize
authors: A M
authors: AM
authors: Poisner
authors: R H
authors: RH
authors: Alper
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D004054:Diethylstilbestrol / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D000077267:Fulvestrant; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D013997:Time Factors
chemical_list: D004965:Estrogen Antagonists; D004967:Estrogens; D004968:Estrogens, Non-Steroidal; D011960:Receptors, Estrogen; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D000077267:Fulvestrant; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D004958:Estradiol; D004054:Diethylstilbestrol; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin