We have examined the spinal cord for the presence of glucocorticoid-binding sites. For this purpose, cytosol from the spinal cord of adrenalectomized rats was incubated with (3H)-dexamethasone. Maximal binding was obtained after 20 h of incubation at 0°C in the presence of 20 mM molybdate, whereas at 20° C the maximum was at 2 h. Using a range of (3H)-dexamethasone concentrations (0.2-30 nM), low capacity (161 ± 23 fmol/g protein) and high affinity (K(d) 3.2 ± 0.3 nM) sites were measured. Binding sites decreased by 25% and K(d) increased 2.5-fold after incubation with a pure glucocorticoid (RU 26988). Relative binding affinities of several competitors of 10 nM (3H)-dexamethasone were: triamcinolone acetonide 108, dexamethasone 100, RU 26988 54, corticosterone 18, progesterone 17, aldosterone 7, estradiol and testosterone < 1. Sedimentation coefficients in glycerol gradients containing molybdate were in the range of those published for glucocorticoid receptors (9.6-9.8 S). Binding of (3H)-dexamethasone was decreased by omitting a SH-protective agent from the buffer or by addition of SH-blocking reagents such as N-ethylmaleimide and p-chloromercuribenzoate. Using rats of different ages, it was found that binding sites were much lower in spinal cord from 2- to 8-day-old rats than in rats of 13-20 days and adults. Regional distribution studies using cytosol from spinal cords dissected between vertebrae C1-C2, C3-C7, T1-T8, T9-L3 and L4-L6 revealed that binding sites were higher in regions containing the cervical (C3-C7) and lumbar (T9-L3) enlargements, with respect to L4-L6. These studies suggest that the spinal cord contains cytosolic-binding sites resembling glucocorticoid receptors, and that the reported action of these steroids on spinal cord function could be mediated by these sites.
Documento: | Artículo |
Título: | Properties and distribution of glucocorticoid-binding sites in cytosol of the spinal cord |
Autor: | Orti, E.; Coirini, H.; De Nicola, A.F. |
Filiación: | Laboratorio de Esteroides, Instituto de Biologia y Medicina Experimental, 1428 Buenos Aires, Argentina |
Palabras clave: | 11beta,17beta dihydroxy 17 (1 propynyl)androsta 1,4,6 trien 3 one; aldosterone; corticosterone; dexamethasone; dexamethasone h 3; estradiol; glucocorticoid receptor; progesterone; radioisotope; testosterone; triamcinolone acetonide; unclassified drug; adrenalectomy; animal cell; article; central nervous system; drug distribution; drug efficacy; drug receptor binding; endocrine system; nonhuman; ontogeny; pharmacokinetics; priority journal; rat; spinal cord |
Año: | 1985 |
Volumen: | 40 |
Número: | 3 |
Página de inicio: | 225 |
Página de fin: | 231 |
DOI: | http://dx.doi.org/10.1159/000124134 |
Título revista: | Neuroendocrinology |
Título revista abreviado: | NEUROENDOCRINOLOGY |
ISSN: | 00283835 |
CODEN: | NUNDA |
CAS: | 11beta,17beta dihydroxy 17 (1 propynyl)androsta 1,4,6 trien 3 one, 74915-58-5; aldosterone, 52-39-1, 6251-69-0; corticosterone, 50-22-6; dexamethasone, 50-02-2; estradiol, 50-28-2; progesterone, 57-83-0; testosterone, 58-22-0; triamcinolone acetonide, 76-25-5 |
Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00283835_v40_n3_p225_Orti |