RESUMO
3H-(+/-) propranolol and 125I-(+/-) cyanopindolol have been used to characterize beta adrenoceptors of liver, lung, kidney and heart of rat. Two main binding parameters, KD and Bmax were measured using either cells, homogenates or plasma membranes of each organ (except heart). Results show that the most accurate determination of KD and Bmax involves: (1) a previous extraction of plasma membranes (2) the use of a ligand of a high affinity for beta adrenoceptors (3) a high specific radioactivity of this ligand. 125I-(+/-) cyanopindolol seems to be a better ligand than 3H(+/-) propranolol for such determinations.
Assuntos
Rim/metabolismo , Fígado/metabolismo , Pulmão/metabolismo , Miocárdio/metabolismo , Pindolol/análogos & derivados , Propranolol/metabolismo , Animais , Membrana Celular/metabolismo , Iodocianopindolol , Cinética , Masculino , Pindolol/metabolismo , Ratos , Ratos Endogâmicos , Receptores Adrenérgicos beta/metabolismoRESUMO
Binedaline (1-[[2-(dimethylamino)ethyl]methylamino]- 3-phenylindole) binding to human alpha 1-acid glycoprotein and other serum proteins was studied in the presence of three basic compounds: chlorpromazine, propranolol, and imipramine. In serum, at therapeutic concentrations, binedaline binding was not modified by the presence of these three compounds, nor did binedaline inhibit the binding of these compounds. With isolated alpha 1-acid glycoprotein, the four drugs exhibited competitive inhibition indicating that they share a common binding site on this protein.
Assuntos
Antidepressivos/sangue , Proteínas Sanguíneas/metabolismo , Indóis/sangue , Orosomucoide/metabolismo , Adulto , Ligação Competitiva/efeitos dos fármacos , Clorpromazina/farmacologia , Diálise , Feminino , Humanos , Imipramina/farmacologia , Masculino , Propranolol/farmacologia , Ligação ProteicaRESUMO
Serum binding of binedaline, a new antidepressant drug, was studied in vitro by equilibrium dialysis. The percent of binding in serum is high, 99.2%, and remains constant within the range of therapeutic concentrations; no saturation to the binding sites was seen. Investigations performed on isolated proteins with a wide range of concentrations showed one site with a high affinity constant (Ka = 2 X 10(6) M-1) for alpha 1-acid glycoprotein and two sites with a low affinity constant (Ka = 3 X 10(4) M-1) for human serum albumin. Binding to lipoproteins was nonsaturable, with a total affinity constant of 1.25 X 10(5) less than nKa less than 2.79 X 10(6) M-1. Over the range of therapeutic concentrations, the ratio of binedaline concentrations in serum and red blood cells remained constant (1%) and was shown to be dependent on the free fraction of binedaline in serum.