A thermodynamic analysis of estrogen regulation of alpha 2-adrenoceptor binding.
Brain Res
; 674(1): 26-32, 1995 Mar 13.
Article
en En
| MEDLINE
| ID: mdl-7773692
ABSTRACT
We previously demonstrated that in vivo estradiol treatment markedly attenuates alpha 2-adrenoceptor function and coupling to G-proteins in the hypothalamus of female rats. Ligand binding studies indicated that 48 h exposure to estradiol decreases the number of alpha 2-adrenergic receptors in the agonist high affinity state. In the present studies, when [3H]RX821002 was used to label brain alpha 2-adrenoceptors, the density of binding sites significantly increased in the hypothalamus and preoptic area 48 h after estrogen treatment. Moreover, the thermodynamics of ligand binding to alpha 2-adrenergic receptors in membranes of female rat hypothalamus were modified by the same estradiol treatments that reduce alpha 2-adrenoceptor function. In hypothalamic membranes from ovariectomized control rats, antagonist (RX821002)-receptor binding was primarily entropy-driven while agonist (oxymetazoline) binding had a higher enthalpy component. In membranes from estradiol-exposed animals, the entropic contribution to both agonist and antagonist bindings was markedly increased, and the enthalpy component was reduced. Since the thermodynamic characteristics of ligand-receptor binding are strongly correlated with efficacy in activating signal transduction [36], these data raise the intriguing possibility that steroids regulate transmembrane signaling by stabilization of a receptor conformation with reduced intrinsic efficacy.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores Adrenérgicos alfa
/
Estradiol
Límite:
Animals
Idioma:
En
Revista:
Brain Res
Año:
1995
Tipo del documento:
Article
País de afiliación:
Estados Unidos