摘要:

To elucidate the role of ATP in histamine release, the present study was performed using β-escin-permeabilized rat peritoneal mast cells. Ca2+-induced histamine release from permeabilized cells is totally dependent upon exogenous ATP in the medium. In the presence of Ca2+, ATP caused histamine release concentration-dependently at concentrations ranging from 0.01 to 5 mmol/l. The maximum release was achieved at 3 mmol/l of ATP in the medium. When the other adenosine nucleotides (AMP, ADP), or nonhydrolyzable ATP analogues (adenylylimidodiphosphate, βγ-methylene ATP) were added in place to ATP, no histamine release took place. Other ribonucleoside triphosphates (GTP, ITP, UTP and CTP) had little effect at the same concentration range. When the ribunucleoside triphosphate content of mast cells was determined by means of HPLC, ITP and CTP were not detectable. A millimolar range of the ATP content was determined in mast cells, but the amounts of other ribonucleoside triphosphates (GTP and UTP) were remarkably lower than that of ATP. These results seem to indicate that the ATP molecule plays a crucial role in histamine release from rat mast cells in association with its concurrent hydrolysis. Furthermore, 12-O-tetradecanoylphorbol-13-acetate and 1-oleoyl-2-acetylglycerol enhanced histamine release elicited in the presence of Ca2+ (0.1 μmol/l) and ATP (3 mmol/l). Calphostin C, a potent inhibitor of protein kinase C, inhibited Ca2+/ATP-dependent histamine release by approximately 60%. At the same concentration, calphostin C inhibited by 95% protein kinase C activity in the crude extract obtained from rat mast cells. It was suggested that protein kinase C activation took place in the Ca2+/ATP-dependent histamine release from permeabilized rat mast ce

ISSN:0031-7012    

DOI:10.1159/000138812

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Caffeine and analogs that contain ethyl, propyl, allyl, propargyl and other substituents in place of methyl at 1-, 3- and 7-positions were antagonists at the two major classes (A1 and A2) of adenosine receptors. Potency at both receptors increased as methyls were replaced with larger substituents. Certain analogs with only one of the three methyl groups of caffeine replaced by larger substituents were somewhat selective for A2 receptors. None of the analogs were particularly selective for A1 receptors. The presence of polar entities in the substituent at the 1- or 7-position was poorly tolerated at adenosine receptors. Activity of caffeine analogs at A1 and A2 adenosine receptors in a variety of systems and cell types is presented and summarized.

ISSN:0031-7012    

DOI:10.1159/000138813

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Omeprazole, a benzimidazole compound which inhibits H+/K+ ATPase in the gut, is used in the treatment of gastroesophageal reflux disease. Clinical and experimental use of omeprazole has been associated with inhibition of the cytochrome P450-dependent metabolism of a few drugs both in vivo in man and in vitro in animals. In these experiments, in vivo administration of omeprazole to rats failed to inhibit the cytochrome P450-dependent metabolism of four prototypic drugs, testosterone or estradiol.

ISSN:0031-7012    

DOI:10.1159/000138814

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Human gastric mucosal cells were isolated by digestion of fundic biopsies with pronase and collagenase. The mean value of gastric cells per milligram biopsy specimen ± SEM was 59,000 ± 4,300 (n = 31) with a viability of 90 ± 5 %. With the cell yield of 1 patient a series of approximately 70 – 80 cyclic AMP measurements was possible. Histamine stimulated intracellular cyclic AMP production with an EC50 value of 35 ± 25 μmol/l (SEM; n = 4). In the presence of 100 μmol/l histamine the Ki values (μmol/l) for the histamine H2 receptor antagonists averaged 1.45 (cimetidine), 0.10 (ranitidine), and 0.02 (famotidine). No significant inhibition of histamine-induced cyclic AMP production was obtained with the histamine H1 receptor antagonist triprolidine. With the new method histamine-induced cyclic AMP production can be measured in intact human gastric mucosal cells from fundic biopsy

ISSN:0031-7012    

DOI:10.1159/000138815

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The purpose of the present study was to investigate the influence of ischemia on postischemic metabolic activity of the brain. Furthermore, the effect of preischemic application of neuroprotective agents such as flunarizine or phencyclidine on postischemic local cerebral glucose utilization (LCGU) was examined. Forebrain ischemia in the rat was performed for 10 min with bilateral carotid clamping, administration of trimethaphan and blood withdrawal to obtain a mean arterial blood pressure of 40 mm Hg. LCGU was determined 7 days after ischemia by injecting 14C-deoxy-D-glucose in saline solution. A significant increase in LCGU in the CA1 subfield of the hippocampus was found 7 days after ischemia, whereas preischemic administration of flunarizine or phencyclidine inhibited this increase. Alterations in LCGU of other brain regions were insignificant.

ISSN:0031-7012    

DOI:10.1159/000138816

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

We evaluated the effect of the RGD-containing peptide, echistatin, on thrombolysis time and acute reocclusion in a canine model of coronary thrombosis/thrombolysis. Occlusive thrombus formation was induced by electrical injury, via a stimulating electrode, to the endothelial surface of the circumflex coronary artery in the open-chest, anesthetized dog in the presence of a critical stenosis. Fifteen minutes after occlusive thrombus formation, dogs received either an intravenous infusion of vehicle (saline at 0.1 ml/min) or echistatin (15 μg/kg/min i.v.). Heparin was given as an initial bolus (100 U/kg i.v.) 15 min after thrombus formation and repeated at hourly intervals (50 U/kg). This dose of heparin increased activated partial thromboplastin time to 1.5- to 2.5- fold over control. Thrombolysis was induced with recombinant tissue-type plasminogen activator (tPA) at a total dose of 1 mg/kg, intravenously administered over 90 min with 10% given as an initial bolus. The vehicle-treated animals reperfused at 48 ± 9 min with a reperfusion incidence of 60% (3/5). The echistatin-treated animals reperfused at 46 ± 5 min with a reperfusion incidence of 100% (5/5). After stopping the tPA infusion, acute reocclusion occurred in 100% (3/3) of the vehicle-treated dogs and in only 20% (1/5) of the echistatin-treated dogs. Echistatin caused a greater than 5-fold increase in buccal mucosa bleeding time and almost completely inhibited ex vivo platelet aggregation to ADP, collagen, and U-46619. Residual thrombus wet weight, determined at the end of the experiment, was significantly lower for the echistatin group (2.1 ± 0.2 mg) compared to the vehicle group (5.8 ± 0.7 mg). These data demonstrate that the antiaggregatory RGD-containing peptide, echistatin, increases the overall incidence of tPA-induced reperfusion and prevents acute reocclusion in this canine model of coronary thromb

ISSN:0031-7012    

DOI:10.1159/000138817

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

This study was designed to assess the effect of chronic dietary administration (2.5 and 5.0% by weight) of the neutral amino acid, L-tryptophan, on the development of hypertension during chronic exposure to cold. In addition, a warm-adapted and cold-treated control group receiving unsupplemented food were used. Chronic administration of the lower dose of L-tryptophan (850 mg/day) prevented the elevation of blood pressure attenuated cardiac hypertrophy, and had no effect on body weight during exposure to cold. The higher dose of L-tryptophan (1,690 mg/day) attenuated the rate of blood pressure increase, did not affect cardiac hypertrophy, attenuated the gain in body weight, and increased the urinary output of epinephrine. Thus, this dose may be associated with some toxicity. Both doses of tryptophan failed to prevent certain other responses characteristically occurring during exposure to cold: i.e. increased weight of the kidneys, adrenal glands and brown adipose tissue; increased food and water consumption; increased dipsogenic responsiveness to angiotensin II, and increased plasma aldosterone concentration. The results indicate that chronic dietary administration of L-tryptophan (850 mg/day) can prevent the development of cold-induced hypertension, as it can in all other models of hypertension tested thus far in rats.

ISSN:0031-7012    

DOI:10.1159/000138818

出版商:S. Karger AG    

年代:1991

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138819

出版商:S. Karger AG    

年代:1991

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138820

出版商:S. Karger AG    

年代:1991

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138811

出版商:S. Karger AG    

年代:1991

数据来源: Karger