Disease relevance of DIHYDROALPRENOLOL

• We have demonstrated that the rat pituitary tumor cell line GH3 has a carrier-mediated active transport system for the beta-adrenergic antagonist dihydroalprenolol (DHA) [1].

High impact information on DIHYDROALPRENOLOL

• The number of beta-adrenergic receptors, as measured by radioligand binding with 3H-labeled dihydroalprenolol, was increased in the frontal cortex and hippocampus of rats with lesions [2].
• Interruption of the ascending noradrenergic neurons of the locus coeruleus in the rat forebrain with 6-hydroxydopamine produced a progressive accumulation, proximal to the lesion, of tritiated dihydroalprenolol binding activity over 2 days [3].
• The density but not the affinity of beta-adrenergic receptors declined significantly with age in rat pineal gland, corpus striatum, and cerebellum, as determined by the binding of tritiated dihydroalprenolol [4].
• Binding properties of the receptor for both agonist and antagonist, as assessed by KD for dihydroalprenolol and Ki for isoproterenol, are normal in CF granulocyte particulates [5].
• The tumor binding sites had high affinity for (-)[3H] dihydroalprenolol with an equilibrium dissociation constant of 2.1 nM [6].

Biological context of DIHYDROALPRENOLOL

• Spielberger State anxiety scores correlated with baseline mean heart rate, and Spielberger Trait anxiety scores with lymphocyte DHA binding [7].
• Using DHA, we demonstrated that the concentration of pulmonary beta-receptors increased significantly between 28 and 31 days of gestation; however, there was no change in the dissociation constant during gestation [8].
• The Kd value for dihydroalprenolol was approximately the same when determined from equilibrium binding studies or from association and dissociation kinetics, suggesting that the ligand binding is a single step bi-molecular reaction [9].
• Down regulation of dihydroalprenolol and imipramine binding sites in brain of rats repeatedly treated with imipramine [10].
• Cold acclimation produced, in isolated cells only, a decrease of 41% in the [3H] dihydroalprenolol binding sites and a beta-adrenergic agonist affinity increase [11].

Anatomical context of DIHYDROALPRENOLOL

• Binding properties of the receptor for both antagonist and agonist, as assessed by KD for dihydroalprenolol and Ki for (-)-isoproterenol, are also normal in the CF lymphocytes [5].
• The equilibrium dissociation constant (KD) for the interaction of receptors with dihydroalprenolol was the same (2 to 15 nM) in membranes from control and hyperthyroid rats [12].
• Crude plasma membranes were prepared from chick lens epithelial and fiber cells and assayed for specific binding of the beta-adrenergic antagonist dihydroalprenolol [13].
• Myocardial beta-adrenoceptor binding was investigated, with (-)3H dihydroalprenolol as radioligand, in microsomes derived from anterior (ALV) and inferior (ILV) myocardial wall sections of the canine left ventricle [14].
• We used [3H] dihydroalprenolol (DHA) to investigate the development of pulmonary beta-adrenergic receptors in rabbit fetuses and to study the effect of glucocorticoid treatment on the beta-receptor number [8].

Associations of DIHYDROALPRENOLOL with other chemical compounds

• No binding of the alpha 1 adrenoceptor antagonist prazosin was observed and the binding properties of beta adrenergic receptors (assayed with 3H-labelled dihydroalprenolol), were similar to those described for normal lymphocytes [15].
• When the concentration of beta-adrenergic receptors was measured by various concentrations of [3H] dihydroalprenolol (DHA), the maximal binding sites of C6 and C6V-1 cells were 760 and 230 fmol/mg protein, respectively, without any changes in the association constant for DHA [16].
• These purified membranes were enriched 25-fold in Na+/K(+)-adenosine triphosphate (ATPase), 37-fold in [3H] dihydroalprenolol binding sites, and fivefold in alkaline phosphatase activity compared with the placenta homogenates [17].
• Moclobemide administered subchronically down-regulates beta adrenoceptors as shown by binding experiments with brain cortical membranes using dihydroalprenolol as ligand [18].
• Transport of DHA in GH3 was saturable, with an apparent Km of 1.4 microM, was temperature and pH dependent, and was inhibited by the ionophore monensin and the amine transport inhibitor reserpine [1].

Gene context of DIHYDROALPRENOLOL

• The present study examined 1) agonist displaceable [3H] dihydroalprenolol (DHA) binding in the neonatal and adult mouse heart and 2) adenylate cyclase in fetal, neonatal and adult mouse heart [19].
• Transient expression of the gene in COS-1 cells resulted in 18 +/- 3 pmol beta2-AR/mg of membrane protein, as measured by saturation binding assay using the beta2-AR antagonist [3H] dihydroalprenolol [20].
• Enrichment of adenylate cyclase activity for BM was 9-fold for N, and enrichment of dihydroalprenolol binding to beta-adrenergic receptors was 12-fold for N and 6-fold for PE, with 14 per cent protein recovery for both N and PE [21].
• Autoradiographic localization of peripheral benzodiazepine, dihydroalprenolol and arginine vasopressin binding sites in the pituitaries of control, stalk transected and Brattleboro rats [22].
• Metoprolol, a purported beta 1-adrenergic specific antagonist, was bound to the receptor with a Ki of approximately 300 nM when the radioligands were CGP or ICP but with a Ki of approximately 1,000 nM when the radioligand was DHA [23].

Analytical, diagnostic and therapeutic context of DIHYDROALPRENOLOL

• Other rats were pre-treated with an intraperitoneal injection of a 500-fold excess of L-isoproterenol prior to the DHA [24].
• Enzyme activity was measured as [3H] thymidine (dThd) monophosphate; mitotic index was determined after tissue staining, and beta-adrenoceptors were quantified by saturation binding of [3H] dihydroalprenolol [25].

References