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Abstract:

High affinity binding of3H-fiunitrazepam (FNZP) to crude membrane preparations of bovine pineal membranes was examined by a rapid filtration procedure through Whatman GFB paper. At 0 °C binding reached equilibrium in about 20 min. Scatchard analysis of data at equilibrium revealed a single population of binding sites with dissociation constant (Kd) = 3.14 ± 0.45 nM and binding site concentration (Bmax) = 55.6 ± 5.6 fmol/mg protein. Kinetic analysis of the association and dissociation curves indicated a kinetic Kd = 1.13 nM, in reasonable agreement to that obtained at equilibrium. When various benzodiazepine (BZP) analogues were tested for their ability to inhibit3H-FNZP binding, the following Ki(nM) were obtained: Clonazepam (0.22), Ro 15-1788(0.48), FNZP (0.95), Ro 5-4864 (> 10,000). When the β-carboline derivative3H-ethyl-β-carboline-3-carboxylate ester (EβCEE) was used as a radioligand, Kd at equilibrium (0.98 nM), kinetic Kd (1.69 n M) and affinity order for analogues were in close agreement to those found for FNZP binding; however, Bmax was about 60% that observed for3H-FNZP binding. Addition of GABA or pentobarbital (100 μM) to pineal membranes increased3H-FNZP binding by 55 and 72%. These results suggest the existence of a mixed population of type 1 and type 2 central BZP receptor subclass in bovine pineal gland. © 1983 S. Karger AG, Basel.

Registro:

Documento: Artículo
Título:Characterization of flunitrazepam and beta-carboline high affinity binding in bovine pineal gland
Autor:Lowenstein, P.R.; Cardinali, D.P.
Filiación:Centro de Estudios Farmacológicos y de Principios Naturales (CEFAPRIN), Buenos Aires, Argentina
Palabras clave:Barbiturates; Benzodiazepine binding; GABA; Pineal gland; β-Carboline binding; 4 aminobutyric acid; 4' chlorodiazepam; barbituric acid derivative; benzodiazepine; clonazepam; flumazenil; flunitrazepam; pentobarbital; radioisotope; animal cell; beta carboline 3 carboxylic acid ethyl ester h 3; cattle; cell membrane; central nervous system; drug receptor binding; endocrine system; flunitrazepam h 3; nonhuman; pharmacokinetics; pineal body; Animal; Anti-Anxiety Agents, Benzodiazepine; Benzodiazepines; Binding Sites; Carbolines; Cattle; Comparative Study; Flunitrazepam; gamma-Aminobutyric Acid; In Vitro; Indoles; Kinetics; Pentobarbital; Pineal Gland; Rats; Species Specificity; Support, Non-U.S. Gov't
Año:1983
Volumen:37
Número:2
Página de inicio:150
Página de fin:154
DOI: http://dx.doi.org/10.1159/000123533
Título revista:Neuroendocrinology
Título revista abreviado:Neuroendocrinology
ISSN:00283835
CAS:4 aminobutyric acid, 28805-76-7, 56-12-2; 4' chlorodiazepam, 14439-61-3; benzodiazepine, 12794-10-4; clonazepam, 1622-61-3; flumazenil, 78755-81-4; flunitrazepam, 1622-62-4; pentobarbital, 57-33-0, 76-74-4; Anti-Anxiety Agents, Benzodiazepine; Benzodiazepines; beta-carboline-3-carboxylic acid ethyl ester, 74214-62-3; Carbolines; Flunitrazepam, 1622-62-4; gamma-Aminobutyric Acid, 56-12-2; Indoles; Pentobarbital, 76-74-4
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00283835_v37_n2_p150_Lowenstein

Referencias:

  • Asano, T., Ogasawara, N., Prostaglandin A as possible endogenous ligand of benzodiazepine receptor, Eur (1982) J. Pharmacol, 80, pp. 271-274
  • Asano, T., Spector, S., Identification of inosine and hypoxanthine as endogenous ligands for brain benzodiazepine-binding sites (1979) Proc. natn. Acad. Sci. USA, 76, pp. 977-981
  • Bennet, J.P., Jr., Methods in binding studies (1978) Neurotransmitter Receptor Binding, pp. 57-90. , Yamamura, H.I.; Enna, S.J.; Kuhar, M.J. editors, (Raven Press, New York)
  • Braestrup, C., Nielsen, M., 3H-propyl-β-carboline-3-carboxylate as a selective radioligand for BZ<inf>i</inf>-benzodiazepine receptor subclass (1981) J. Neurochem, 37, pp. 333-341
  • Braestrup, C., Nielsen, M., Olsen, C.E., Urinary and brain β-carboline-3-carboxylates as potent inhibitors of brain benzodiazepine receptors (1980) Proc. natn. Acad. Sci. USA, 77, pp. 2288-2292
  • Chabot, G., Brissette, Y., Gascon, A.L., Relationship between plasma corticosterone and adrenal epinephrine after diazepam treatment in rats (1982) J. Physiol. Pharmacol, 60, pp. 589-596
  • Chan, A., Ebadi, M., The kinetics of norepinephrine-induced stimulation of serotonin-N-acetyltransferase in bovine pineal gland (1980) Neuroendocrinology, 31, pp. 244-251
  • Costa, T., Rodbard, D., Pert, C.B., Is the benzodiazepine receptor coupled to a chloride anion channel? Nature (1979) Lond, 277, pp. 315-317
  • Cowen, P.J., Green, A.R., Nutt, D.J., Ethyl-β-carboline carboxylate lowers seizure threshold and antagonizes flurazepam-in-duced sedation in rats (1981) Nature, Lond, 290, pp. 54-55
  • Ebadi, M., Chan, A., Characteristics of GABA binding sites in bovine pineal gland (1980) Brain Res. Bull, 5, pp. 179-187
  • Ehlert, F.J., Rogan, P., Chen, A., Roeske, W.R., Yamamura, H.I., Modulation of benzodiazepine receptor binding: Insight into pharmacological efficacy (1982) Eur. J. Pharmacol, 78, pp. 249-253
  • Farrell, G., McLsaac, W.M., Adrenoglomerulotropin (1961) Archs Biochem, 94, pp. 543-544
  • Fehske, K.J., Zube, I., Borbe, H.O., Wollert, U., Müller, W.E., β-Carboline binding indicates the presence of benzodiazepine receptor subclasses in the bovine central nervous system (1982) Arch. Pharmacol, 319, pp. 172-177
  • Fujimoto, M., Kawasaki, K., Matsushita, A., Okabayashi, T., Ethyl-β-carboline-3-carboxylate reverses the diazepam effect on cerebellar cyclic GMP (1982) Eur. J. Pharmacol, 80, pp. 259-262
  • Grandison, L., Suppression of prolactin secretion by benzodiazepines in vivo (1982) Neuroendocrinology, 34, pp. 369-373
  • Grandison, L., Cavagnini, F., Schmid, R., Invitti, C., Guidotti, A., γ-Aminobutyric acid-and benzodiazepine-binding sites in human anterior pituitary tissue (1982) J. clin. Endocr. Metab, 54, pp. 597-601
  • Hirsch, J.D., Kochman, R.L., Summer, P.B., Heterogeneity of brain benzodiazepine receptors demonstrated by JH-propyl-β- carboline-3-carboxylate binding (1982) Molec. Pharmacol, 21, pp. 618-628
  • Kari, I., 6-Methoxy-l,2,3,4-tetrahydro-β-carboline in pineal gland of chicken and cock (1981) FEBS Lett, 127, pp. 277-280
  • Klein, D.C., Auerbach, D.A., Weller, J.L., Seesaw signal processing in pineal cells: Homologous sensitization of adrenergic stimulation of cyclic GMP accompanies homologous desensitization of β-adrenergic stimulation of cyclic AMP (1981) Proc. natn. Acad. Sci. USA, 78, pp. 4625-4629
  • Lotz, W., Benzodiazepine antagonist Ro 15-1788 counteracts the prolactin-lowering effects of other benzodiazepine in rats (1982) Neuroendocrinology, 35, pp. 32-36
  • Lowenstein, P.R., Cardinali, D.P., Benzodiazepine receptor sites in bovine pineal (1983) Eur. J. Pharmacol, 86, pp. 287-289
  • Mata, M., Schrier, B.K., Klein, D.C., Weller, J.L., Chiou, C.Y., On GABA function and physiology in the pineal gland (1976) Brain Res, 118, pp. 383-394
  • McLsaac, W.M., Formation of l-methyl-6-methoxy-l,2,3,4-tetrahydro-β-carboline under physiological conditions (1961) Biochim. biophys. Acta, 52, pp. 607-609
  • Möhler, H., Polc, P., Cumin, R., Pieri, L., Kettler, R., Nicotinamide is a brain constituent with benzodiazepine-like actions (1979) Nature, Lond, 278, pp. 563-565
  • Müller, W.E., The benzodiazepine receptor, an update (1981) Pharmacology, 22, pp. 153-161
  • Olsen, R.W., GABA-benzodiazepine-barbiturate receptor interactions (1981) J. Neurochem, 37, pp. 1-13
  • Pole, P., Ropert, N., Wright, D.M., Ethyl-β-carboline-3-carboxylate antagonizes the action of GABA and benzodiazepines in the hippocampus (1981) Brain Res, 217, pp. 216-220
  • Racagni, G., Apud, J.A., Cocchi, D., Locatelli, V., Müller, E.E., Gabaergic control of anterior pituitary hormone secretion (1982) Life Sci, 31, pp. 823-838
  • Rommelspacher, H., The β-carbolines (harmanes) - a new class of endogenous compounds. Their relevance for the pathogenesis and treatment of psychiatric and neurological diseases (1981) Pharmacopsychiatry, 14, pp. 117-125
  • Skolnic, P., Marangos, P.J., Goodwin, F.K., Edwards, M., Paul, S., Identification of inosine and hypoxanthine as endogenous inhibitors of 3H-diazepam binding in the central nervous system (1978) Life Sci, 23, pp. 1473-1480
  • Speth, R.C., Guidotti, A., Yamamura, H.I., The pharmacology of benzodiazepines (1981) Neuropharmacology of Central Nervous System and Behavioral Disorders, pp. 244-283. , Palmer, G.C., editor, (Academic Press, New York)
  • Tallman, J.F., Mallorga, P., Thomas, J.W., Gallager, D.W., Benzodiazepine binding sites. Properties and modulation (1981) GABA and Benzodiazepine Receptors, pp. 9-18. , Costa, E.; di Chiara, G.; Gessa.G.L., editors, (Raven Press, New York)
  • Waniewski, R.A., Suria, A., Modulation of cyclic GMP in the rat pineal gland by GABA (1980) Brain Res. Bull, 5, pp. 347-354
  • Williams, L.T., Lefkowitz, R.J., (1978) Receptor binding in adrenergic pharmacology, , (Raven Press, New York)

Citas:

---------- APA ----------
Lowenstein, P.R. & Cardinali, D.P. (1983) . Characterization of flunitrazepam and beta-carboline high affinity binding in bovine pineal gland. Neuroendocrinology, 37(2), 150-154.
http://dx.doi.org/10.1159/000123533
---------- CHICAGO ----------
Lowenstein, P.R., Cardinali, D.P. "Characterization of flunitrazepam and beta-carboline high affinity binding in bovine pineal gland" . Neuroendocrinology 37, no. 2 (1983) : 150-154.
http://dx.doi.org/10.1159/000123533
---------- MLA ----------
Lowenstein, P.R., Cardinali, D.P. "Characterization of flunitrazepam and beta-carboline high affinity binding in bovine pineal gland" . Neuroendocrinology, vol. 37, no. 2, 1983, pp. 150-154.
http://dx.doi.org/10.1159/000123533
---------- VANCOUVER ----------
Lowenstein, P.R., Cardinali, D.P. Characterization of flunitrazepam and beta-carboline high affinity binding in bovine pineal gland. Neuroendocrinology. 1983;37(2):150-154.
http://dx.doi.org/10.1159/000123533