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Biomedical subjects

J Kunert-Radek

Publications and source records attributed to J Kunert-Radek.

At least 55 records · Page 3Linked to original sources

Inhibition of cell proliferation of human gliomas by benzodiazepines in vitro.

The effects of several benzodiazepines (diazepam, clonazepam, Ro 15-1788 and Ro 5-4864) on cell proliferation of 2 human gliomas were estimated in vitro by means of [3H]-thymidine uptake assay. It was found that all tested benzodiazepines suppressed [3H]-thymidine incorporation into the DNA of glioma cells, the effects being stronger in case of peripheral-type benzodiazepine receptor ligands. The results indicated that benzodiazepines might exert an antiproliferative action on glioma tumour cells growth.

Astrocytoma↗

Influence of somatostatin and epidermal growth factor (EGF) on the proliferation of follicular cells in the organ-cultured rat thyroid.

The effects of somatostatin (SS), epidermal growth factor (EGF), as well as interactions among SS, EGF, and TSH in their action on the proliferation of thyroid follicular cells (TFC) in organ culture were investigated. It was shown that (1) SS (10(-7) M) decreased significantly the mean mitotic activity rate (MMAR) of TFC; (2) SS (10(-7) M) suppressed the mitogenic TSH action on the TFC proliferation; and (3) TSH, as well as EGF, caused an elevation of MMARs of TFC, the effect of TSH, however, being much stronger than that of EGF. The acquired data suggest that SS, most probably by paracrine interaction, may inhibit the mitotic activity of TFC. The mitogenic effect of EGF, a potent mitogen for TFC in cell culture, is not so strongly expressed in organ culture.

Animals↗

Somatostatin suppression of meningioma cell proliferation in vitro.

Considering the presence of a stereospecific receptor for somatostatin (SST) in human meningioma cells and the possible involvement of this neuropeptide in the growth control of certain meningioma cell lines, the effects of SST on the proliferation of human meningioma cells in vitro was investigated. Tumour tissues for primary cell cultures were obtained surgically from 2 women with histopathological diagnosis of meningothelial meningioma. The incorporation of [3H]-thymidine into meningioma cells DNA was measured as an index of the cells proliferation. It was shown that SST (10(-7)-10(-5) M) significantly inhibited the [3H]-thymidine incorporation. The results have indicated that SST may have an antiproliferative effects on the meningioma tumour cells in vitro.

Adult↗

Immunomodulatory action of somatostatin.

The influence of somatostatin (SST) on spontaneous proliferation and cyclic AMP level in mouse spleen lymphocytes and on inhibition of human leukocyte migration was studied. The rate of [3H]thymidine incorporation was used as an index of proliferation. It was found that lower concentrations of SST/10(-9) and 10(-8)M, inhibited the splenocyte proliferation. In contrast, a higher SST concentration, 10(-7)M, exerted a stimulatory effect. SST in concentrations from 10(-9) to 10(-6)M did not influence cyclic AMP levels in mouse splenocytes; a significant decrease of cyclic AMP was found after the exposure to superactive SST analog RC-102-2H in concentrations 10(-8) and 10(-7)M. SST, 10(-7)M, and RC-102-2H, 10(-7)M, significantly enhanced the migration inhibition of human leukocytes induced by the exposure of leukocytes to cardiac antigen or phytohemagglutinin. The data provide evidence for an immunomodulatory action of SST.

Adjuvants, Immunologic↗

Enhancement of estradiol-induced DNA synthesis in the anterior pituitary gland by the peripheral-type benzodiazepine receptor ligand Ro 5-4864.

The effects of peripheral (Ro 5-4864) and central-type (Ro 15-1788) benzodiazepine receptor ligands on estrogen-induced DNA synthesis in the rat anterior pituitary gland was investigated. As expected, a single injection of estradiol (250 micrograms per rat) significantly increased the uptake of 3H-thymidine by anterior pituitary cells. Additional treatment with Ro 5-4864 potentiated the effects of estradiol on pituitary DNA synthesis. Under the same experimental conditions, no effect of Ro 15-1788 and sodium valproate, a GABA-transaminase inhibitor, was detected. These findings indicate the involvement of peripheral-type benzodiazepine receptors in the control of anterior pituitary cell proliferation.

Animals↗

Rat hypothalamus contains an antimitogenic factor acting via benzodiazepine receptors.

The effect of crude rat hypothalamic extracts on the lymphocyte proliferation in vitro was investigated. It was found that hypothalamic extracts (HE) significantly inhibited the 3H-thymidine incorporation by the mouse spleen lymphocytes cultured in vitro. The factor (or factors) responsible for the antimitogenic effect is thermostabile and partially destroyable by trypsin digestion. The latter observation suggests that it is probably a peptide. Diazepam had been found to exert a similar antimitogenic effect on mouse spleen lymphocytes as HE. The putative endogenous benzodiazepine (BZD) receptor ligand is also assumed to be a peptide. The working hypothesis that the antimitogenic effect of HE depends on endogenous substance acting via BZD receptor was proposed. To test such a possibility, the interaction of HE and specific BZD receptor ligands Ro-15-1788 and Ro-5-4864 was investigated. It was found that Ro-5-4864 alone suppressed the lymphocyte proliferation, and the joint antiproliferative effect of HE and Ro-5-4864 was not additive. Ro-15-1788 alone did not influence the lymphocyte proliferation but abolished the antiproliferative effect of HE. These data suggest that antimitogenic factor present in HE acts via BZD receptors.

Animals↗

Effect of somatostatin on the proliferation of mouse spleen lymphocytes in vitro.

The effect of somatostatin on the spontaneous proliferation of mouse spleen lymphocytes was investigated in vitro. The rate of 3H-thymidine incorporation was used as an index of lymphocyte proliferation. Somatostatin in a concentration of 10(-7) M enhanced the lymphocyte proliferation and abolished the antiproliferative effect of rat hypothalamic extract. Lower concentrations of somatostatin slightly decreased the lymphocyte DNA synthesis.

Animals↗

Influence of melatonin and serotonin on the number of rat pineal "synaptic" ribbons and spherules in vitro.

Previous studies have shown that the "synaptic" ribbons (SR) and spherules (SS) of the mammalian pineal gland may respond differently under physiological and various experimental conditions. The aim of the present study was to gain insight into the mechanisms that may be responsible for the numerical changes of these organelles during a 24-h cycle. As the possibility exists that the structures are influenced by substances synthesized within the pinealocyte, rat pineal glands were cultured with and without added melatonin or serotonin, using an experimental protocol such that the addition of melatonin and serotonin mimicks the circadian changes of the respective substances within the pineal. The tissue was processed for electron microscopy and the numbers of SR and SS were counted in a unit area of pineal tissue. The results obtained indicate that melatonin added to the incubation medium increases the number of SR in the first half of the night; serotonin decreases SR numbers in the morning. SS numbers, by contrast, decrease following melatonin administration in the afternoon, and increase in the morning following serotonin administration. It thus appears that the numbers of SR and SS are influenced by melatonin and serotonin and that the two structures are regulated by differential, but nevertheless biochemically closely related mechanisms.

Animals↗

Colloid droplet accumulation precedes the enhancement of 6-keto-PGF 1 alpha release from the thyrotropin-stimulated thyroid gland.

Influence of thyrotropin (TSH) on colloid droplet formation in thyroid follicular cells and on release of a stable prostacyclin metabolite, 6-keto-prostaglandin 1 alpha (6-keto-PGF 1 alpha) from the thyroid has been studied in rats. Maximal accumulation of colloid droplets preceded the enhancement of the 6-keto-PGF 1 alpha release. Such a time sequence speaks against the possibility of prostacyclin involvement in the thyroid secretory response to TSH.

6-Ketoprostaglandin F1 alpha↗

Effects of dopamine on cyclic AMP concentration in the anterior pituitary gland in vitro.

Effects of different concentrations of dopamine on the cyclic AMP concentration in the anterior pituitary gland were investigated in vitro. Low concentrations of dopamine (10(-9)--10(-8) mol/l) were found to decrease, whereas the high concentration (10(-5) mol/l) increased the cyclic AMP concentration in pituitaries collected from ovariectomized and estradiol-treated females. In contrast, dopamine had no effect on the anterior pituitary cAMP concentration when pituitaries were collected from ovariectomized rats which had not received estrogen replacement. These data show that the action of dopamine on the anterior pituitary cAMP largely depends on the dopamine concentration and the hormonal state of animals.

Animals↗