title: Involvement of norepinephrine activity in the regulation of alpha 1 adrenergic receptors in the medial preoptic nucleus of estradiol-treated rats.
abstract: To establish whether the diurnal decrease in the density of alpha 1 receptors observed in the medial preoptic nucleus (MPN) of estrogen (E2)-treated rats is related to the concomitant diurnal increase in norepinephrine (NE) turnover rates, we quantitated the density of [3H]-Prazosin binding to alpha 1 receptors after blockade of NE turnover with alpha-methyl-paratyrosine (alpha MPT). A series of preliminary studies was performed to rule out an interference of this drug with [3H]-Prazosin binding to alpha 1 adrenergic receptors in vitro and in vivo. Incubation of brain slices with alpha MPT produced a dose-dependent inhibition of [3H]-Prazosin binding to alpha 1 adrenergic receptors with an IC50 of approximately 6 mM. Scatchard analysis demonstrated that alpha MPT exhibited a simple competitive interaction with [3H]-Prazosin binding sites as shown by an increase in the apparent dissociation constant (Kd) of the ligand and no change in the number of alpha 1 receptors (Bmax). In contrast, preincubation of brain slices with alpha MPT and prior in vivo administration of alpha MPT did not affect [3H]-Prazosin binding to alpha 1 adrenergic receptors. Once we established that alpha MPT could be used to suppress NE turnover without interfering with the measurement of alpha 1 receptor densities, we repeatedly injected this drug to ovariectomized (OVX) and E2-implanted rats. The density of alpha 1 adrenergic receptors in MPN was quantitated autoradiographically. Blockade of NE turnover with alpha MPT only partially prevented the reduction in alpha 1 receptor density observed in the E2-treated rats, suggesting that the decrease in the level of [3H]-Prazosin binding sites cannot be completely ascribed to increased NE turnover rates.
authors.affiliation: Department of Physiology, University of Maryland, School of Medicine, Baltimore 21201.
authors.forename: M A
authors.initials: MA
authors.lastname: Sortino
authors.forename: N G
authors.initials: NG
authors.lastname: Weiland
authors.forename: P M
authors.initials: PM
authors.lastname: Wise
mesh_terms: D000818:Animals; D002940:Circadian Rhythm; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D008781:Methyltyrosines / Q000494:pharmacology*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000502:physiology*; D010052:Ovariectomy; D011224:Prazosin / Q000378:metabolism; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D019805:alpha-Methyltyrosine
chemical_list: D008781:Methyltyrosines; D011942:Receptors, Adrenergic, alpha; D004958:Estradiol; D019805:alpha-Methyltyrosine; D009638:Norepinephrine; D011224:Prazosin