ABSTRACT
Serotonin, acetylcholine and noradrenaline neither initiated nor indicated the uterus contractility in immature or pregnant mice; they, however, regulated the uterine motility in respect to the neurotransmitters concentration and the hormonal status of females. Inactivation of the beta-receptors in longitudinal muscle fibres prevented the drop in the myometric contraction force, whereas blockade of the alpha-receptors in circular muscle fibres prevented the reduction of the myometric tone induced by noradrenaline. The data obtained suggests that the circular muscle is responsible for the myometric tone while the longitudinal muscle is responsible for the uterus contraction force.
Subject(s)
Acetylcholine/pharmacology , Norepinephrine/pharmacology , Pregnancy, Animal/physiology , Serotonin/physiology , Uterine Contraction/physiology , Acetylcholine/physiology , Adrenergic Antagonists/pharmacology , Animals , Female , Mice , Muscarinic Antagonists/pharmacology , Muscle, Smooth/drug effects , Muscle, Smooth/physiology , Norepinephrine/physiology , Pregnancy , Receptors, Adrenergic, alpha/drug effects , Receptors, Adrenergic, alpha/physiology , Receptors, Adrenergic, beta/drug effects , Receptors, Adrenergic, beta/physiology , Receptors, Muscarinic/drug effects , Receptors, Muscarinic/physiology , Receptors, Serotonin/drug effects , Receptors, Serotonin/physiology , Serotonin/pharmacology , Serotonin Antagonists/pharmacology , Time Factors , Uterine Contraction/drug effectsSubject(s)
Adrenergic alpha-Agonists/pharmacology , Muscle Contraction/physiology , Norepinephrine/pharmacology , Pregnancy, Animal/physiology , Receptors, Adrenergic, alpha/physiology , Uterus/physiology , Animals , Female , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Muscle Contraction/drug effects , Pregnancy , Signal Transduction , Uterus/drug effectsSubject(s)
Pregnancy, Animal/physiology , Uterine Contraction/physiology , Animals , Female , Male , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , PregnancyABSTRACT
We have examined the role of serotonin, a neurotransmitter, in the development of normal embryos and embryos irradiated in utero at different stages of morpho- and organogenesis. We have found that serotonin is capable of attenuating radiation-induced disturbances of development; serotonin therapeutic action varied depending on the age of the embryo, severity of the original radiation damage, and the time that serotonin was administered after irradiation. All data provide evidence that the window of serotonin's therapeutic effect is strictly timed to a certain stage of prenatal ontogenesis, specifically, to neurogenesis. This conclusion is in agreement with the view that serotonin serves as a morphogenetic signal for the developing nervous system, the state of which is important for the viability and functionality of fetuses in the normal state and after exposure to ionizing irradiation.
Subject(s)
Embryonic and Fetal Development/drug effects , Embryonic and Fetal Development/radiation effects , Radiation-Protective Agents/pharmacology , Serotonin/pharmacology , Animals , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Female , Gestational Age , Male , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Pregnancy , Serotonin/physiologySubject(s)
Embryonic and Fetal Development/radiation effects , Radiation Injuries, Experimental/prevention & control , Radiation-Protective Agents/therapeutic use , Serotonin/therapeutic use , Animals , Drug Administration Schedule , Female , Male , Mice , Mice, Inbred C57BL , Radiation-Protective Agents/administration & dosage , Serotonin/administration & dosageABSTRACT
In the experiments with Ehrlich ascites tumor cells it was shown that specific oxidation of cellular glutathione after irradiation produced no effect on the degree of radiation injury in the air, but resulted in a decrease of radioprotective effect of beta-mercaptoethylamine. From these results it follows that for a complete realization of radioprotective effect normal level of cellular glutathione is necessary.
Subject(s)
Cysteamine/pharmacology , Diamide/pharmacology , Radiation Injuries, Experimental/drug therapy , Animals , Carcinoma, Ehrlich Tumor/drug therapy , Carcinoma, Ehrlich Tumor/metabolism , Cysteamine/therapeutic use , Diamide/therapeutic use , Drug Evaluation, Preclinical , Drug Interactions , Glutathione/drug effects , Glutathione/metabolism , Glutathione/radiation effects , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Oxidation-Reduction/drug effects , Oxidation-Reduction/radiation effects , Radiation Injuries, Experimental/metabolism , Tumor Cells, Cultured/drug effects , Tumor Cells, Cultured/metabolism , Tumor Cells, Cultured/radiation effectsABSTRACT
In experiments with Ehrlich ascites tumor cells, using a specific thiol blocker, 6,6'-dithiodinicotinic acid, that does not penetrate the cell and therefore only binds SH-groups of peripheral areas of an external cell membrane, it was demonstrated that (1) the external cell membrane is the site where the radioprotective effect of anoxia (the oxygen effect) is realised (2) thiols of the external cell membrane contribute markedly to the oxygen effect, and (3) they are needed at both stages of its realization.
Subject(s)
Hypoxia/metabolism , Radiation-Protective Agents , Sulfhydryl Compounds/metabolism , Animals , Carcinoma, Ehrlich Tumor/metabolism , Cell Membrane/drug effects , Cell Membrane/metabolism , Cell Membrane/radiation effects , Chromosome Aberrations , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Nicotinic Acids/pharmacology , Sulfhydryl Compounds/radiation effects , Sulfhydryl Reagents/pharmacology , Tumor Cells, CulturedABSTRACT
It was shown on Ehrlich ascites tumor cells that for realization of the radioprotective effect of anoxia and beta-mercaptoethylamine normal content of glutathione is necessary not only at the time of irradiation but in the postirradiation period as well while glutathione content should be normal only after irradiation for realization of the radiotherapeutic effect of serotonin.
Subject(s)
Carcinoma, Ehrlich Tumor/radiotherapy , Glutathione/metabolism , Radiation-Protective Agents , Animals , Carcinoma, Ehrlich Tumor/genetics , Carcinoma, Ehrlich Tumor/metabolism , Chromosome Aberrations/drug effects , Chromosome Aberrations/radiation effects , Mice , Oxygen/pharmacology , Radiation Tolerance , Serotonin/pharmacology , Time FactorsABSTRACT
A study was made of the influence of binding of endogenous nonprotein thiols (glutathione, GSH) by N-ethylmaleimide before or after irradiation (7 Gy) of Ehrlich ascites tumor cells on the radioprotective effect of anoxia (argon, 0.003% O2). It was shown that the radioprotective effect of anoxia decreased as cell glutathione was removed before or after irradiation (similarly both immediately and 1 h after irradiation). Inspite of the fact that the GSH level decreased similarly before and after irradiation the radioprotective effect of anoxia was less pronounced in the latter case. The data obtained permit to evaluate quantitatively the contribution of endogenous GSH to the processes occurring at the time of irradiation and during the post-irradiation period.
Subject(s)
Glutathione/radiation effects , Oxygen Consumption/radiation effects , Animals , Argon , Carcinoma, Ehrlich Tumor/metabolism , Cells, Cultured , Chromosome Aberrations , Glutathione/metabolism , Hypoxia/metabolism , Time FactorsABSTRACT
In experiments on Ehrlich ascite tumor cells, the dependence of the radioprotective effect of beta-mercaptoethylamine and beta-mercaptopropionylglycine on the initial level of endogenous glutathione was studied. A varying degree of N-ethylmaleimide induced decrease of SH-glutathione content in the cells led to either easing or elimination of the radioprotective effect of the agents under study.
Subject(s)
Carcinoma, Ehrlich Tumor/radiotherapy , Glutathione/metabolism , Radiation Tolerance , Radiation-Protective Agents/pharmacology , Animals , Carcinoma, Ehrlich Tumor/metabolism , Dose-Response Relationship, Radiation , Mercaptoethylamines/pharmacology , Mice , Tiopronin/pharmacologyABSTRACT
5-HT applied prior to, immediately or 5 min after irradiation decreased equally the radiation damage to Ehrlich ascite tumor cells. A decrease in the endogenous glutathione content by N-ethylmaleimide (NEM) led to reduced the 5-HT radio-modifying effect. Its radio-modifying effect decreased irrespective of whether NEM was applied prior to or after irradiation.
