Binding and effects of catecholestrogens on adenylate cyclase activity, and adrenoceptors, benzodiazepine and GABA receptors in guinea-pig hypothalamic membranes

Catecholestrogen (CE) binding to guinea-pig hypothalamic membranes was assessed by using [3H]2-hydroxyestrone (2-OHE2) as a ligand. Binding was maximal at pH 7.4 and 37°C, and after 10 min incubations. A high affinity binding site with dissociation constant (KD) = 0.20 ± 0.02 nM and site concentrati...

Descripción completa

Guardado en:
Detalles Bibliográficos
Publicado: 1986
Materias:
Adenylate cyclase
Adrenoceptor binding
Benzodiazepine binding
Catecholestrogens
GABAergic binding
Hypothalamus
2 hydroxyestradiol
2 hydroxyestrone
2 hydroxyestrone h 3
4 aminobutyric acid h 3
4 aminobutyric acid receptor
adenylate cyclase
adrenalin
alpha adrenergic receptor
benzodiazepine receptor
beta adrenergic receptor
catechol estrogen
dihydroalprenolol h 3
dihydroergocryptine h 3
domperidone
dopamine
estradiol
estrone
flunitrazepam h 3
noradrenalin
phentolamine
propranolol
radioisotope
unclassified drug
animal cell
article
central nervous system
drug binding
drug receptor binding
guinea pig
hypothalamus
nervous system
nonhuman
pharmacokinetics
priority journal
synaptosome
Adenylate Cyclase
Animals
Binding, Competitive
Cell Membrane
Enzyme Activation
Estrogens, Catechol
Guinea Pigs
Norepinephrine
Receptors, Adrenergic
Receptors, GABA-A
Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00142999_v129_n1-2_p1_Etchegoyen
http://hdl.handle.net/20.500.12110/paper_00142999_v129_n1-2_p1_Etchegoyen
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:Catecholestrogen (CE) binding to guinea-pig hypothalamic membranes was assessed by using [3H]2-hydroxyestrone (2-OHE2) as a ligand. Binding was maximal at pH 7.4 and 37°C, and after 10 min incubations. A high affinity binding site with dissociation constant (KD) = 0.20 ± 0.02 nM and site concentration (Bmax) = 38 ± 2 fmol/mg protein, and a low affinity binding site with KD = 235 ± 10 nM and Bmax = 4.2 ± 1.0 pmol/mg protein (n = 7) were detected. The order of affinity (Ki, μM) for displacement of 10 nM [3H]2-OHE1 from hypothalamic binding sites was 2-OHE1 (0.8), 2-hydroxyestradiol (2-OHE2) (1.0), epinephrine (5.9), norepinephrine (NE) (7.7), dopamine (270), estradiol, estrone, propranolol, phentolamine, domperidone (>10 000). NE inhibition of 2-OHE1 binding was non-competitive, Only 0.5 mM 2-OHE2 depressed in a non-competitive way the hypothalamic β-adrenoceptor binding (measured by using [3H]dihydroalprenolol) without affecting α-adrenoceptor binding (measured by using [3H]dihydroergocryptine). Both 2-OHE2 and 2-OHE1 impaired NE-stimulated adenylate cyclase activity in hypothalamic membranes with EC50 of about 5 and 10 μM, respectively. CE decreased [3H]γ-aminobutyric acid binding by hypothalamic membranes with Ki = 8 μM (2-OHE2) and 50 μM (2-OHE1). The binding of [3H]flunitrazepam to the same membrane preparation was not affected by CE. These results support the existence of significant CE binding and effects in guinea-pig hypothalamic membranes. © 1986.

Ejemplares similares