RESUMO
The effect of various radiation doses on membrane reception of prostaglandin E2(PGE2) of spleen, small intestine, brain, and liver cells of mice was studied in dynamics. Irradiation of the animals with doses producing bone marrow, intestinal and cerebral forms of radiation sickness was shown to change specific binding of PGE2 to cell membranes of both radiosensitive tissues and a relatively radioresistant organ, the liver.
Assuntos
Prostaglandinas E/metabolismo , Lesões Experimentais por Radiação/metabolismo , Receptores de Prostaglandina/metabolismo , Animais , Encéfalo/metabolismo , Dinoprostona , Relação Dose-Resposta à Radiação , Intestino Delgado/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Baço/metabolismoRESUMO
The contribution of the post-irradiation changes in prostaglandin transformation to the biochemical mechanism of interphase death of irradiated cells is estimated. It is supposed that prostaglandins are secondary trigger-effectors which initiate the development of primary biochemical reactions giving rise to radiation sickness. It is suggested that the biochemical mechanism of interphase death is complex and involves several concurrent trigger mechanisms including prostaglandin regulation system.
Assuntos
Sobrevivência Celular/efeitos da radiação , Interfase/efeitos da radiação , Prostaglandinas/fisiologia , AnimaisRESUMO
Prostaglandin E2 (PGE2) was specifically bound by the membrane fraction prepared from the mouse liver. The binding constants indicate the presence of high-affinity PGE2 binding sites with an apparent dissociation constant (Kd) of 0.82 X 10(-9) M and a capacity of 0.36 X 10(9) M/mg protein and a lower affinity PGE2 binding site with Kd = 15.73 X 10(-9) M and a capacity of 5.31 X 10(9) M/mg protein. The radioprotectors, MEA and APAETP inhibit PGE2 binding and alter its kinetics. Apparently the mechanism of PGE2 binding by membranes is related to interaction of prostaglandins with thiols and sufhydryl groups of membrane lipoproteins, while the radioprotectors modify the functional groups participating in receptor PGE2 binding.
Assuntos
Fígado/efeitos dos fármacos , Prostaglandinas E/metabolismo , Protetores contra Radiação/farmacologia , Receptores de Superfície Celular/efeitos dos fármacos , Receptores de Prostaglandina/efeitos dos fármacos , Amifostina/farmacologia , Animais , Dinoprostona , Cinética , Fígado/metabolismo , Masculino , Mercaptoetilaminas/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Ligação Proteica/efeitos dos fármacos , Receptores de Prostaglandina/metabolismo , Receptores de Prostaglandina ERESUMO
After intraperitoneal administration of beta-mercaptoethylamine (MEA) into mice of F1 strain (CBA XC57B1) at a radioprotective dose, activity of PGE2 and PGF2 alpha-synthetases was decreased in liver microsomes, testicular and brain supernatants (16,000xg) within 15 min, which corresponded to period of the highest radioprotector activity. Amount of newly synthesized prostaglandins was increased in liver tissue within the subsequent periods. Within 3 hrs after the radioprotector administration these amounts constituted for PGE2 246% and for PGF2 alpha 262% as compared with controls; at the same time, activity of PG-synthetases in testes was normalized. In the brain tissue within 1 hr the newly synthesized prostaglandins amounted to 121% for PGE2 and 125% for PGF2 alpha, within 3 hrs they decreased to control values. Decrease in activity of PGE2 and PGF2 alpha-synthetases was shown to depend on MEA concentration in vitro. Possible mechanisms of the radioprotector effect at various steps of the prostaglandins biosynthesis are discussed.
Assuntos
Mercaptoetilaminas/farmacologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Prostaglandinas E/biossíntese , Prostaglandinas F/biossíntese , Animais , Encéfalo/enzimologia , Depressão Química , Radicais Livres , Técnicas In Vitro , Masculino , Camundongos , Microssomos Hepáticos/enzimologia , Glândulas Seminais/enzimologiaAssuntos
Encéfalo/enzimologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Lesões Experimentais por Radiação/enzimologia , Animais , Medula Óssea/efeitos da radiação , Dinoprosta , Dinoprostona , Intestinos/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Sistema Nervoso/efeitos da radiação , Prostaglandinas E/biossíntese , Prostaglandinas F/biossínteseAssuntos
Encéfalo/efeitos da radiação , Cruzamentos Genéticos , Fígado/efeitos da radiação , Prostaglandina-Endoperóxido Sintases/efeitos da radiação , Testículo/efeitos da radiação , Animais , Encéfalo/enzimologia , Ativação Enzimática/efeitos da radiação , Raios gama , Fígado/enzimologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Testículo/enzimologia , Fatores de TempoAssuntos
Ansiolíticos/farmacologia , Benzodiazepinas , Benzodiazepinonas/farmacologia , Encéfalo/metabolismo , Prostaglandinas E/biossíntese , Prostaglandinas F/biossíntese , Animais , Dimetil Sulfóxido/farmacologia , Hibridização Genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Estimulação QuímicaRESUMO
Effect of various concentrations of a radioprotector S-[N-(3 aminopropyl)-2-aminoethyl] thiophosphoric acid on the activity of prostaglandine synthetase was studied in mouse liver microsomes as well as in the soluble fractions of testicules and brain in vitro. The activity of prostaglandine synthetase was estimated by monitoring the formation of labelled PGF2 alpha and PGE2 from I-14C-arachidonic acid. The radioprotector at concentration 1.66 mg/ml stimulated formation of PGF2 alpha in all the tissues studied. At the lower concentrations of the radioprotector only slight stimulation of the biosynthesis of prostaglandines in testicules was noted. No effect on their synthesis in the brain soluble fraction could be observed while in the liver microsomes it was inhibited. The radioprotective substance studied apparently affected the cyclooxygenase activity, which is a key enzyme in the prostaglandine-synthesizing system.