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141.
Susanne Berglund Bryan J. Egner Henrik Gradén Joakim Gradén David G.A. Morgan Tord Inghardt Fabrizio Giordanetto 《Bioorganic & medicinal chemistry letters》2009,19(15):4268-4273
Herein, we disclose the discovery and optimization of 2-piperidin-4-yl-acetamide derivatives as MCH-R1 antagonists. Structural investigation of piperidin-4-yl-amide and piperidin-4-yl-ureas identified 2-piperidin-4-yl-acetamide-based MCH-R1 antagonists with outstanding in vivo efficacy but flawed with high affinity towards the hERG potassium channel. While existing hERG SAR information was employed to discover highly potent MCH-R1 antagonists with minimized hERG inhibition, additional hurdles prevented their subsequent clinical exploration. 相似文献
142.
R Trouvé G Nahas C Latour 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1992,201(2):215-218
Sprague-Dawley rats were fitted under pentobarbital anesthesia with a catheter in the caudal artery and their carotid arteries were exposed. The pressure signal from the caudal artery was treated on line by a microcomputer for continuous display of blood pressure and heart rate measurements. The animals were administered intraperitoneally either 50 mg/kg of cocaine or an equal volume of saline. Five minutes later, stimulation of the baroreflex was performed by bilateral clamping of the two carotids for a period of 2 min. The same maneuver was repeated at 12, 24, and 31 min. Analysis of variance for repeated measures indicated that before carotid artery clamping, there was no significant difference between blood pressure measurements of the saline- and cocaine-treated groups. A two-factor analysis of variance of the repeated measures of the maximal variation in systolic pressure after each clamping showed a significant difference between control and cocaine-administered groups (P < 0.001), with the former displaying a much greater increment in blood pressure after carotid clamping. Cocaine exerts an inhibitory effect on the baroreflex that may be mediated through the increased angiotension II caused by the alkaloid. 相似文献
143.
144.
E Burzawa-Gérard B Delevallée-Fortier 《Comptes rendus de l'Académie des sciences. Série III, Sciences de la vie》1992,314(9):411-416
The effect of different preparations of growth hormone (GH) was assayed with 17 beta-estradiol on vitellogenesis in hypophysectomized or normal female silver eels. Vitellogenin (Vg) plasma levels were taken as the index of hepatic vitellogenesis. The E2 doses were chosen to give the same pattern for the plasma Vg level as in the controls. They decreased or remained undetectable in hypophysectomized or normal animals. GH also failed to induce alone a significant modification. When E2 was injected together with a GH, plasma Vg levels were 5.13 +/- 1.30 times higher with salmon GH in hypophysectomized eels and 2.01 +/- 0.25 times higher with bovine GH in normal eels. GH is shown to enhance the effects of E2 on hepatic vitellogenesis induction in a teleost. 相似文献
145.
146.
The metabolic fate of 1-O-[3H]alkyl-2-acetyl-sn-glycero-3-phosphorylcholine ([3H]-AGEPC) upon interaction with rabbit platelets was investigated. [3H]AGEPC was converted to a product identified as the long-chain fatty acyl analog. The reaction was unaffected by extracellular calcium. After a lag time of 30 to 60 s the kinetics of the conversion was linear. The rate of the reaction was found to be a function of platelet and AGEPC concentrations. Of the [3H]AGEPC (10?9m) 85 ± 5% was processed into the-long chain fatty acyl analog within 1 h when incubated at 37 2C with a 1.25 × 109 platelets per milliliter suspension. A maximal number of 1200 to 3600 [3H]AGEPC molecules were converted to the long-chain fatty acyl derivative per minute per platelet in the presence of 2 mm EDTA. Under similar conditions the 1-O-[3H]alkyl-2-(lyso)-sn-glycero-3-phosphorylcholine ([3H]lysoGEPC) also was transformed to a comparable long-chain fatty acyl derivative at a much slower rate and to a lower extent. No significant increase in lysoGEPC was noted in incubation mixtures containing [3H]AGEPC. The possible direct transacylation of AGEPC upon interaction with platelets is discussed as well as the possible involvement of this reaction in directly triggering the platelet response to AGEPC stimuli. 相似文献
147.
The effect of primycin, a guanidine-type antibiotic was studied on the electric properties and 42K+ uptake of the frog sartorius and semitendinosus muscle. Both in normal and choline chloride Ringer solution, primycin evoked a concentration and time dependent depolarization of the surface membrane of the muscle. This depolarization was significantly increased by Na ions. Primycin treatment was shown to evoke a dose-dependent decrease of the depolarization induced by 20 mM K+-Ringer. When the muscles were incubated in a Ringer solution containing choline chloride, during an incubation period of 30 min the uptake of 42K+ was decreased to 12% upon the exposure to 5 x 10(-6) mol primycin as compared to the control value. As the primycin-induced depolarization increased, the shape and amplitude of the action potentials elicited by square-wave electric impulses were altered and decreased, respectively. In sodium isaethionate Ringer 1--2 x 10(-6) M primycin induced a slow depolarization resulting in firing potentials. The results suggest that primycin depolarizes the surface membrane exclusively through the blockade of the resting K+ channels, the other phenomena being the results of this depolarizing effect. 相似文献
148.
Staining and histochemical methods, immunofluorescence, and electron microscopy were used to individualize the prolactin cells in the adenohypophyseal pars distalis of the nonhibernating hedgehog. One cell type was differentiated; their characteristics at the light and electron microscopic levels were presented. Immunofluorescence has confirmed the functional significance of this cell type and the validity of the denomination 'prolactin cells'. 相似文献
149.
V Carillet P Morlière J C Mazière G Hüppe R Santus L Dubertret 《Biochimica et biophysica acta》1990,1055(2):102-106
Etretinate or acitretin are efficiently delivered to cultured human fibroblasts in the presence of low density lipoproteins, high density lipoproteins or human serum albumin. In contrast to acitretin, delivery of etretinate to fibroblasts is more efficiently achieved with human serum albumin than with lipoproteins. The uptake of etretinate and acitretin via low density lipoproteins delivery, does not take place via the low density lipoprotein-receptor endocytotic pathway but mostly through a passive exchange with the plasma membrane. However, in contrast to acitretin, the exchange of etretinate seems to occur alter binding of etretinate-loaded low density lipoproteins to the apolipoprotein B receptors. No differences are observed in binding, internalization and degradation of native, etretinate-loaded low density lipoproteins and acitretin-loaded low density lipoproteins, suggesting that the presence of these retinoids in low density lipoproteins does not alter their processing by the cells. Furthermore, the presence of these retinoids in the cells does not notably affect, under our experimental conditions, the catabolism of native low density lipoproteins. 相似文献
150.