RESUMEN
We studied endogenous phosphorylation in rat transplantable MT/W9A hormone-dependent mammary tumors of untreated rats and of animals treated with LH-RH analogs, the agonist D-Trp-6-LH-RH and the antagonist N-Ac-D-p-Cl-Phe1,2,D-Trp3,D-Arg6,D-Ala10-LH-RH. Incorporation of 32P from 32P-ATP was reduced significantly in tumors of rats treated with agonistic and antagonistic analogs of LH-RH or ovariectomized. The inhibition of protein phosphorylation may be related to tumor regression.
Asunto(s)
Hormona Liberadora de Gonadotropina/análogos & derivados , Neoplasias Mamarias Experimentales/metabolismo , Proteínas de Neoplasias/metabolismo , Animales , Autorradiografía , Femenino , Hormona Liberadora de Gonadotropina/farmacología , Neoplasias Hormono-Dependientes/metabolismo , Ovariectomía , Radioisótopos de Fósforo , Fosforilación , Ratas , Ratas Endogámicas WF , Pamoato de TriptorelinaRESUMEN
We investigated phosphorylation in Dunning R-3327H prostate tumor tissue of untreated rats, and rats treated with the agonist D-Trp6-LH-RH and antagonist N-Ac-D-p-Cl-Phe1,2,D-Trp3,D-Arg6,D-Ala10-LH-RH. The total phosphorylation was significantly higher in Dunning tumors than in normal ventral and dorsal prostate. Incorporation of 32P into tumor tissue of rats treated with D-Trp6-LH-RH was significantly lower than in tumors from untreated animals. The tumor regression produced by LH-RH agonist appeared to be linked with changes in the pattern of tumor protein phosphorylation. Although inhibition of tumor growth also occurred after administration of the LH-RH antagonist, no significant changes in phosphorylation were observed. The dissimilarity of effects of the agonists and the antagonists on protein phosphorylation in rat prostate tumors may be related to the differences in the mechanisms of action of these two types of LH-RH analogues.
Asunto(s)
Hormona Liberadora de Gonadotropina/análogos & derivados , Proteínas de Neoplasias/metabolismo , Fosfoproteínas/metabolismo , Neoplasias de la Próstata/metabolismo , Animales , Hormona Liberadora de Gonadotropina/uso terapéutico , Masculino , Fosforilación , Neoplasias de la Próstata/tratamiento farmacológico , Ratas , Pamoato de TriptorelinaRESUMEN
Some small peptides, ACTH sequences, are able to modify the 32P incorporation in brain proteins in vitro. The possibility that these peptides play a role in the regulation mechanism of some brain functions through differentiated protein-kinases could be considered.
Asunto(s)
Hormona Adrenocorticotrópica/farmacología , Encéfalo/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Fragmentos de Péptidos/farmacología , Fosfatos/metabolismo , Animales , Técnicas In Vitro , Oligopéptidos/farmacología , RatasAsunto(s)
Bucladesina/análogos & derivados , Conjuntivitis/tratamiento farmacológico , 3',5'-AMP Cíclico Fosfodiesterasas/metabolismo , Animales , Bucladesina/uso terapéutico , Conjuntivitis/enzimología , AMP Cíclico/fisiología , Proteínas del Ojo/metabolismo , Cinética , Masculino , Inhibidores de Fosfodiesterasa/farmacología , Ratas , Ratas EndogámicasRESUMEN
Various 8-substituted cAMP analogues were converted into the corresponding N6,O2'-dibutyryl, N6-monobutyryl, or O2'-monobutyryl derivatives and the parent compounds as well as the new derivatives were tested for TSH-like stimulation of the thyroid function in mice in vivo by means of the McKenzie bioassay. It was found that a pronounced stimulatory effect on the thyroid secretion can be produced by certain cyclic nucleotides. The most potent compounds, 8H2N-cAMP, 8MeS-cAMP, and 8N3-cAMP at 15-30 mg/kg iv, showed an activity approximately one order of magnitude higher than that of cAMP and comparable to the action of 0.6-1.0 mU of TSH per mouse iv. Radioimmunological determination of thyroxine levels in the serum confirmed these results. Serum T4 levels in mice injected, for instance, with 8MeS-cAMP (30 mg/kg) rose from 4.85 +/- 0.25 to 6.32 +/- 0.41 mug/100 ml in 1 h, the net increase in T4 being comparable to that produced by TSH (1 mU/mouse) under identical experimental conditions. Introduction of one or two butyryl groups (in the N6 and/or O2' position) significantly increased or decreased the biological activity, dependent on the parent compound, but no direct correlation between biological activity and degree of butyrylation was apparent. The effect of these compounds on the thyroid seems to be specific for cyclic nucleotides because 8MeS-5'AMP which resembles 8MeS-cAMP but lacks the cyclic phosphate structure is inactive in the McKenzie bioassay and in the T4 radioimmunoassay.
Asunto(s)
AMP Cíclico/análogos & derivados , Nucleótidos Cíclicos/síntesis química , Glándula Tiroides/fisiología , Animales , AMP Cíclico/farmacología , Femenino , Masculino , Ratones , Nucleótidos Cíclicos/farmacología , Estimulación Química , Glándula Tiroides/efectos de los fármacos , Tirotropina , Tiroxina/sangreAsunto(s)
AMP Cíclico/administración & dosificación , Psoriasis/tratamiento farmacológico , Teofilina/administración & dosificación , Administración Tópica , Bucladesina/administración & dosificación , Bucladesina/análogos & derivados , Ensayos Clínicos como Asunto , Femenino , Humanos , Inyecciones , MasculinoAsunto(s)
AMP Cíclico/análogos & derivados , Prolactina/metabolismo , Aminoácidos/metabolismo , Animales , Bucladesina/farmacología , Butiratos/farmacología , Radioisótopos de Carbono , AMP Cíclico/farmacología , Electroforesis en Gel de Poliacrilamida , Femenino , Técnicas In Vitro , Adenohipófisis/efectos de los fármacos , Prolactina/biosíntesis , Ratas , Tasa de Secreción/efectos de los fármacos , Estimulación Química , Relación Estructura-Actividad , Compuestos de Sulfhidrilo/farmacologíaAsunto(s)
AMP Cíclico/farmacología , Hormona del Crecimiento/biosíntesis , Hipófisis/efectos de los fármacos , Prolactina/biosíntesis , Animales , Butiratos/farmacología , Radioisótopos de Carbono , Electroforesis en Gel de Poliacrilamida , Femenino , Técnicas In Vitro , Masculino , Hidrolasas Diéster Fosfóricas/farmacología , Ratas , Sulfuros/farmacologíaRESUMEN
Cholinesterase activity of brain and content of growth hormone and prolactin in the pituitary were compared after short-term (3 days) and long-term (14 days) treatment with paraoxon in male and female rats. Within 3 days cholinesterase activity was reduced to between 5 and 15 percent of that in controls. The content of growth hormone in the pituitary was increased in long-term experiments by 50 percent. This increase in paraoxon-treated animals-suggests a possible role of a cholinergic mechanism in the regulation of growth hormone secretion.