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971.
The ATP-dependent uptake of L-glutamate into synaptic vesicles has been well characterized, implicating a key role for synaptic vesicles in glutamatergic neurotransmission. In the present study, we provide evidence that vesicular glutamate uptake is selectively inhibited by the peptide-containing halogenated ergot bromocriptine. It is the most potent inhibitor of the agents tested: the IC50 was determined to be 22 microM. The uptake was also inhibited by other ergopeptines such as ergotamine and ergocristine, but with less potency. Ergots devoid of the peptide moiety, however, such as ergonovine, lergotrile, and methysergide, had little or no effect. Although bromocriptine is known to elicit dopaminergic and serotonergic effects, its inhibitory effect on vesicular glutamate uptake was not mimicked by agents known to interact with dopamine and serotonin receptors. Kinetic data suggest that bromocriptine competes with glutamate for the glutamate binding site on the glutamate translocator. It is proposed that this inhibitor could be useful as a prototype probe in identifying and characterizing the vesicular glutamate translocator, as well as in developing a more specific inhibitor of the transport system. 相似文献
972.
The effects of artificial photoperiod, temperature, and long-term testosterone treatment on testicular luteinizing hormone (LH) binding were studied in adult male Djungarian hamsters. In hamsters transferred to long-day (LD; 16 hr light, 8 hr dark) photoperiod 8 weeks after adaptation in short-day (SD; 8 hr light, 16 hr dark) photoperiod of 25 degrees C, testicular growth was associated with an increase in the total LH binding per two testes and a decrease in LH binding per unit testicular weight. Plasma testosterone levels reached a peak 47 days after transfer to LD and tended to decrease thereafter, while the testes continued growing. In contrast, when hamsters reared under LD conditions at 25 degrees C for 12 weeks were transferred to SD, testicular regression was associated with a decrease in plasma testosterone and the total LH binding per two testes and an increase in LH binding per unit testicular weight. A significant decrease in LH binding per unit weight compared to SD controls was observed in those hamsters exposed to SD with continuous testosterone treatment. The testosterone treatment tended to induce decrease in the total LH binding. Scatchard plot analyses of the binding suggested that changes in LH binding were due to changes in the number of binding sites. When sexually mature male hamsters were subjected for 8 weeks to two different ambient temperatures (7 degrees C and 25 degrees C) and photoperiods (LD and SD), the difference between the two temperature groups was statistically not significant regarding the weights of testes, epididymides, and prostates; plasma testosterone levels; and LH binding in either LD or SD group. These results suggest that photoperiod is a more important environmental factor than temperature for the regulation of testicular activity and LH receptors and that testosterone reduces the number of LH receptors per unit testicular weight in adult male Djungarian hamsters. 相似文献
973.
Takahiro Shimizu Takuto Fujii Hironao Ohtake Toshie Tomii Ryuta Takahashi Kentaro Kawashima Hideki Sakai 《Journal of cellular physiology》2020,235(12):9589-9600
Cisplatin is a widely used platinum-based anticancer drug in the chemotherapy of numerous human cancers. However, cancer cells acquire resistance to cisplatin. So far, functional loss of volume-sensitive outwardly rectifying (VSOR) Cl− channels has been reported to contribute to cisplatin resistance of cancer cells. Here, we analyzed protein expression patterns of human epidermoid carcinoma KB cells and its cisplatin-resistant KCP-4 cells. Intriguingly, KB cells exhibited higher β-actin expression and clearer actin filaments than KCP-4 cells. The β-actin knockdown in KB cells decreased VSOR Cl− currents and inhibited the regulatory volume decrease (RVD) process after cell swelling. Consistently, KB cells treated with cytochalasin D, which depolymerizes actin filaments, showed smaller VSOR Cl− currents and slower RVD. Cytochalasin D also inhibited cisplatin-triggered apoptosis in KB cells. These results suggest that the disruption of actin filaments cause the dysfunction of VSOR Cl− channels, which elicits resistance to cisplatin in human epidermoid carcinoma cells. 相似文献
974.
Plasma levels of glibenclamide in diabetic patients during its routine clinical administration determined by a specific radioimmunoassay 总被引:1,自引:0,他引:1
Plasma concentration of glibenclamide in routine clinical practice was determined by a specific radioimmunoassay. In diabetic patients treated with glibenclamide for a month or longer, the drug level in fasting morning plasma was variable but the mean level paralleled the daily dose. After oral administration of 2.5 mg in healthy and diabetic subjects, the drug level reached peaks in 1.5 hours and declined to the half of the peak level in next 2-3 hours. The plasma glibenclamide profile after oral dose did not differ significantly in patients with secondary failure to the drug. Comparison of a single-dose and divided-dose schedules of 5 mg glibenclamide revealed that plasma drug level increased each time after administration. Plasma glucose and insulin concentrations did not differ significantly at most times of the day but there was a tendency that increment of plasma glucose after meal was suppressed by a dose taken immediately before a meal. The relationship of blood level of glibenclamide to clinical effectiveness may be rather indirect and needs to be elucidated. 相似文献
975.
976.
The suppressive effects of anti-allotype antibody on splenic lymphocytes of adult (>3 months of age) and newborn (1-week-old) rabbits were compared in vitro. An approximately 10-fold lower concentration of anti-b4 sufficed to modulate completely membrane-bound b4 immunoglobulin (Ig) when newborn cells were pulse-treated for 2 or 24 hr than when adult cells were tested. In contrast to splenic lymphocytes from adults, which regenerated most of the original proportion of b4+ cells in culture following treatment with up to 300 μg of anti-b4 for 24 hr (4), immature lymphocytes were susceptible to irreversible modulation of membrane-bound Ig even when lower concentrations of anti-b4 were used. However, under conditions permitting reversible modulation of membrane b4, lymphocytes of newborns regenerated the membrane product more rapidly than did adult cells. Both mature and immature splenocytes were shown to be capable of some level of b4 synthesis even in the continuing presence of anti-b4. No evidence for susceptibility to complement-mediated killing of newborn spleen cells by anti-allotypic antibodies was obtained. The observations reported here support the concept that the greater sensitivity of B lymphocytes from the newborn to succumb to irreversible suppressive effects by anti-allotype antibody plays a significant role in the restriction for induction of allotype suppression to the perinatal period. 相似文献
977.
978.
Effect of prolactin on the testicular luteinizing hormone binding was studied in a serum-free culture system. By the collagenase
digestion of decapsulated testes taken out from 25-day-old rats, Leydig cells were isolated and cultured for 7 days in DME/F12
(1:1) medium supplemented with insulin, transferrin, epidermal growth factor, and gentamicin. The cultured cells exhibited
the 3β-hydroxysteroid dehydrogenase activity. Hill plots constructed from the data of competition experiment showed that the
dissociation constant (Kd) was 0.33 × 10–10M. The Kd value was approximately the same as the known value for the rat testicular homogenates. When the Leydig cells were cultured
with ovine prolactin for the last 3 days of 7-day culture period, the binding of luteinizing hormone increased to 1.7-fold
ofthat in the control group. From these results it is concluded that prolactin acts to up-regulate the binding of luteinizing
hormone to rat testicular Leydig cells in serum-free culture 相似文献
979.
980.