摘要:

Rats were treated intraperitoneally with a mixture of 250 mg/ kg L-DOPA and 40 mg/kg carbidopa or with vehicle and sacrificed 30 min later. Plasma, heart and cortex, midbrain, brain-stem and cerebellum were removed from each animal and assayed by HPLC for L-DOPA and a large number of amino acids and related amino compounds. L-DOPA levels increased from undetectable (<0.2 nmol/ml or g) to 1,146, 1,007, 399, 376, 368 and 850 nmol/ml or g in the above tissues. In addition, several amino compounds were significantly affected by L-DOPA/carbidopa (p < 0.01). Plasma concentrations of phosphoserine, oxidized glutathione, citrulline, phenylalanine, tyrosine and 1-methylhistidine increased and arginine, glutamic acid and lysine decreased. In the heart, concentrations of phosphoserine, taurine, reduced glutathione, threonine, serine, glutamine, glycine, alanine, valine, GABA, ethanolamine, ammonia and arginine decreased. In the cortex, carnosine and homocarnosine increased. In the midbrain, valine increased and leucine, ornithine and oxidized glutathione decreased. In the cerebellum, citrulline increased. In the brainstem, threonine, serine, asparagine, glutamine, oxidized glutathione, alanine, and leucine decreased. In the brainstem, arginine was slightly decreased with a concomitant increase in citrulline (p < 0.05), indicative of nitrous oxide formation. These results show that administration of L-DOPA/ carbidopa not only raises dopamine levels but can also affect other biochemicals and that the observed changes in amino acids and related compounds can perhaps contribute to the beneficial and/or adverse effects of L-DOPA/carbidopa therapy of Parkinson’s diseas

ISSN:0031-7012    

DOI:10.1159/000139518

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The influence of hyperthyroidism on the functional vascular responsiveness of isolated coronary and renal resistance vessels was investigated. Hyperthyroidism was established by feeding rats for 1 and 4 weeks with 5 mg/kg L-thyroxine (T4)-containing rat chow. Preparations of either coronary or renal resistance vessels were mounted in an isometric wire myograph. Subsequently, concentration-effect curves were determined for the effects of 5-hydroxytryptamine (5-HT), 9,11-dideoxy-11α,9α-epoxymethanoprostaglandin F2α (U46619) and isoproterenol in coronary vessels, and for those of meth-oxamine, U46619 and isoproterenol in renal vessel preparations. Our results indicate that hyperthyroidism does not induce major changes in the sensitivity of both coronary and renal resistance vessels towards 5-HT, U46619 and methoxamine. A clearly sensitizing influence of acute hyperthyroidism (1 week of T4 treatment) was found for isoproterenol-induced relaxant responses, whereas hyperthyroidism for 4 weeks did not influence the responses mediated by isoproterenol in coronary resistance arteries. Furthermore, the isoproterenol-induced relaxation in renal arteries was not influenced by the chronic hyperthyroid state of the animal. The present results indicate that in acute hyperthyroidism β-adrenoceptor-mediated vasodilation is increased. However, in chronic hyperthyroidism changes in responsiveness to vasoconstrictor or vasodilator agents of coronary and renal resistance arteries appear not to play a major role. The influence of hyperthyroidism on the functional response of resistance arteries appears to be both tissue and time depend

ISSN:0031-7012    

DOI:10.1159/000139519

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The effect of aminoguanidine (AG) on the expression of adhesion molecules on nonactivated human umbilical vein endothelial cells (HUVEC) was investigated in vitro. Nonactivated HUVEC cultivated on long-term glycated fibronectin (FN) as compared to native FN showed a significant upregulation of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and CD 31 which could be further promoted by long-term glycated bovine serum albumin. AG, at a concentration of 0.01 mol/l, caused an upregulation of ICAM-lof48 ± 17.4% in HUVEC cultivated on gelatin. In contrast, VCAM-1 and E-selectin remained unaffected. At this concentration, formation of advanced glycation end products (AGE) was inhibited by 57%, as determined immunologically, and by 50%, as verified by AGE-specific fluorescence. A hypothesis concerning the upregulation of ICAM-1 by AG as compared to VCAM-1 is proposed relating to its relative redox insensitivity. Our results demonstrate that the beneficial effect of AG in reducing the risk of accelerated development of atherosclerosis in diabetic patients by inhibiting formation of AGE on matrix proteins such as FN might be hampered by its tendency to upregulate ICAM-1 on endothelial cells

ISSN:0031-7012    

DOI:10.1159/000139520

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Previous studies have demonstrated that calcium storage and release from IP-3-dependent sites in the sarcoplasmic reticulum play an important role in the contractile response of the rabbit urinary bladder to both field stimulation (mediated via neurotransmitter release) and bethanechol (direct muscarinic stimulation). In view of the importance of SERCA in urinary bladder smooth muscle function, we studied the distribution of SERCA by two methods: using Western blotting to quantitate the protein concentration and by enzyme analysis using thapsigargin to specifically inhibit SERCA. Rabbit and human samples of urinary bladder smooth muscle were homogenized and the homogenate separated into three particulate fractions by differential centrifugation: nuclear-cell wall, mitochondrial, and microsomal. The protein concentration of these three particulate fractions was determined and the SERCA protein level quantitated by Western blotting using SERCA-2 antibodies. The calcium-ATPase activity was quantitated using standard enzymatic analysis and the thapsigargin sensitivity determined. The results demonstrated that: (1) the concentration of SERCA was significantly greater in the microsomal fraction than in either of the other fractions for both rabbit and human bladder smooth muscle; (2) the enzymatic activities of both total calcium-activated ATPase and thapsigargin-sensitive calcium ATPase were evenly divided among the three fractions, and (3) the enzymatic activity of both total calcium-activated ATPase and thapsigargin-sensitive calcium ATPase of the rabbit exceeded that of the human. In conclusion, the distribution of SERCA and calcium-ATPase of the rabbit bladder smooth muscle was similar to that in the human bladder smooth muscle, although activities in rabbit were significantly greater than those of human tissue.

ISSN:0031-7012    

DOI:10.1159/000139521

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Electrophysiological experiments were carried out to investigate the prokînetic actions of DQ-2511 on isolated smooth muscle of the guinea pig stomach. DQ-2511 enhanced the myogenic gastric slow waves and cholinergic excitatory junction potential and reduced the frequency of slow waves and the nonadrenergic, noncholinergic, and nonnitrergic inhibitory junction potential, with no significant alteration of the resting membrane potential. The results suggest that the prokînetic actions of DQ-2511 involve excitatory actions directly on smooth muscle and indirectly on cholinergic transmissio

ISSN:0031-7012    

DOI:10.1159/000139522

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

We investigated the effects of cimetidine on acute gastric mucosal injury induced by ischemia-reperfusion in rats. Under pentobarbital anesthesia, the celiac artery was clamped for 30 min and reperfused for 60 min. Cimetidine, famotidine and omeprazole caused a dose-dependent suppression in the total area of erosions that were induced by ischemia-reperfusion. Whereas, none of them inhibited the increase in thiobarbituric acid-reactive substances in the stomach, as an index of lipid peroxidation. The inhibitory effect of intraperitoneally administered cimetidine on mucosal damage was abolished by continuous luminal perfusion with HC1 solution (pH 1.5, 1 ml/min) during ischemia-reperfusion, while luminal perfusion with the solution containing HC1 and cimetidine (3 mmol/l) significantly reduced the total area of erosions compared to luminal perfusion with HC1 solution alone. Cimetidine (3 mmol/l) inhibited hydroxyl radical-induced lipid peroxidation of human erythrocyte membranes by 60% in vitro. These results indicate that cimetidine possesses a protective effect against acute gastric mucosal injury induced by ischemia-reperfusion not only due to the suppression in gastric acid secretion, but also due to the antioxidant action when it is present at a high concentration in the intragastric environment.

ISSN:0031-7012    

DOI:10.1159/000139523

出版商:S. Karger AG    

年代:1997

数据来源: Karger