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21.
D. Ukena C. G. Schirren K. -N. Klotz U. Schwabe 《Naunyn-Schmiedeberg's archives of pharmacology》1985,331(1):89-95
Summary Adenosine receptors in guinea pig lung were characterized by measurement of cyclic AMP formation and radioligand binding. 5-N-Ethylcarboxamidoadenosine (NECA) increased cyclic AMP levels in lung slices about 4-fold over basal values with an EC50 of 0.32 mol/l. N6-R-(–)-Phenylisopropyladenosine (R-PIA) was 5-fold less potent than NECA. 5-N-Methylcarboxamidoadenosine (MECA) and 2-chloroadenosine had EC50-values of 0.29 and 2.6 mol/l, whereas adenosine and inosine had no effect. The adenosine receptors in guinea pig lung can therefore be classified as A2 receptors. Several xanthine derivatives antagonized the NECA-induced increase in cyclic AMP levels. 1,3-Diethyl-8-phenylxanthine (DPX; K
i 0.14 mol/l) was the most potent analogue, followed by 8-phenyltheophylline (K
i 0.55 mol/l), 3-isobutyl-1-methylxanthine (IBMX; K
i 2.9 mol/l) and theophylline (K
i 8.1 mol/l). In contrast, enprofylline (1 mmol/l) enhanced basal and NECA-stimulated cyclic AMP formation. In addition, we attempted to characterize these receptors in binding studies with [3H]NECA. The K
D for [3H]NECA was 0.25 mol/l and the maximal number of binding sites was 12 pmol/mg protein. In competition experiments MECA (K
i 0.14 mol/l) was the most potent inhibitor of [3H]NECA binding, followed by NECA (K
i 0.19 mol/l) and 2-chloroadenosine (K
i 1.4 mol/l). These results correlate well with the EC50-values for cyclic AMP formation in lung slices. However, the K
i-values of R-PIA and theophylline were 240 and 270 mol/l, and DPX and 8-phenyltheophylline did not compete for [3H]NECA binding sites. Therefore, a complete characterization of A2 adenosine receptors by [3H]NECA binding was not achieved. In conclusion, our results show the presence of adenylate cyclase-coupled A2 adenosine receptors in lung tissue which are antagonized by several xanthines. 相似文献
22.
Martin J. Lohse Sabine Böser Karl-Norbert Klotz Ulrich Schwabe 《Naunyn-Schmiedeberg's archives of pharmacology》1987,336(2):211-217
Summary The effects of barbiturates on the GABA-receptor complex and the A1 adenosine receptor were studied. At the GABA-receptor complex the barbiturates inhibited the binding of [35S]t-butylbicyclophosphorothionate ([35S]TBPT) and enhanced the binding of [3H]diazepam. Kinetic and saturation experiments showed that both effects were allosteric. Whereas all barbiturates caused complete inhibition of [35S]TBPT binding, they showed varying degrees of maximal enhancement of [3H]diazepam binding; (±)methohexital was identified as the most efficacious compound for this enhancement. At the A1 adenosine receptor all barbiturates inhibited the binding of [3H]N6-phenylisopropyladenosine ([3H]PIA) in a competitive manner. The comparison of the effects on [3H]diazepam and [3H]PIA binding showed that excitatory barbiturates interact preferentially with the A1 adenosine receptor, and sedative/anaesthetic barbiturates with the GABA-receptor complex. It is speculated that the interaction with these two receptors might be the basis of the excitatory versus sedative/anaesthetic properties of barbiturates.Abbreviations GABA
-aminobutyric acid
- TBPT
t-butylbicyclophosphorothionate 1073
- DMBB
5-(1,3-dimethyl)butyl-5-ethylbarbituric acid
- MCB
N-methyl-5-(1-cyclohexen-1-yl)-5-ethylbarbituric acid
- MPPB
N-methyl-5-phenyl-5-propylbarbituric acid
- PIA
N6-phenylisopropyladenosine
Send offprint requests to M. J. Lohse at the above address 相似文献
23.
24.
New anastomosis technique for (laparoscopic) instrumental small-diameter anastomosis 总被引:3,自引:1,他引:2
O. Schöb R. Schmid R. Schlumpf H. P. Klotz M. Spiess F. Largiadèr 《Surgical endoscopy》1995,9(4):444-449
This study presents a new technique for visceral anastomosis. The principle consists of connecting the two parts to be anastomosed around a reabsorbable stent which is transluminally introduced into a small-diameter viscus, where it is fixed. Advancing a larger tube along the axis of the machine, the larger, perforated viscus is inverted and pulled over the stent, and finally a rubber band pops off the machine endoluminally in order to fix the intestinal walls in seroserosal contact onto the stent. To evaluate this micro anastomosis, a biliary bypass (choledochojejunostomy and roux-en-y-loop) was performed in ten pigs. Nine of ten animals showed biliary bypass with good runoff in contrast radiography and completely reabsorbed stent after a 3-month follow-up. Weight gain, bilirubin, and alkaline phosphatase were normal. This technology demonstrates a safe and quick way to perform instrumental micro anastomosis without remnant foreign material.Presented as a poster at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons (SAGES), Nashville, TN, USA, 18–19 April 1994 相似文献
25.
26.
Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine derivatives as highly potent and selective human A(3) adenosine receptor antagonists 总被引:1,自引:0,他引:1
Baraldi PG Cacciari B Romagnoli R Spalluto G Klotz KN Leung E Varani K Gessi S Merighi S Borea PA 《Journal of medicinal chemistry》1999,42(22):4473-4478
27.
K.-N. Klotz E. Camaioni R. Volpini S. Kachler S. Vittori G. Cristalli 《Naunyn-Schmiedeberg's archives of pharmacology》1999,360(2):103-108
A number of 2-substituted 5'-N-ethylcarboxamidoadenosine (NECA) derivatives was investigated for their affinity and selectivity at human A3 adenosine receptors. The compounds were tested in radioligand competition studies and modulation of adenylyl cyclase activity on membranes from CHO cell lines stably transfected with the four human adenosine receptor subtypes. In binding studies the most potent compound, 2-(3-hydroxy-3-phenyl)propyn-1-yl-NECA (PHPNECA), exhibited a subnanomolar affinity for A3 adenosine receptors with a Ki value of 0.4 nM. As opposed to the limited A3 selectivity of PHPNECA, a 100-fold selectivity compared to both A1 and A2A receptors was found for 2-(2-phenyl)ethynyl-NECA (PENECA; Ki 6 nM). The EC50 values for activation of adenylyl cyclase via A2A adenosine receptors were in good agreement with the respective Ki values from binding experiments. In contrast, IC50 values for A1 and A3 receptor-mediated inhibition of adenylyl cyclase were shifted to higher values compared to the respective affinities determined in radioligand competition studies. Similar discrepancies between binding and functional data have been observed for the inhibitory A1 adenosine receptor in previous studies. Therefore, the same A3 selectivity of PENECA compared to A1 receptors was found in binding and adenylyl cyclase inhibition whereas the selectivity compared to A2A receptors that was detected in ligand binding was obscured in the functional assay. The series of compounds presented in this study identifies 2-substitution of the purine system as a promising target for the development of A3-selective high-affinity ligands. 相似文献
28.
S. Larry Goldenberg Laurence H. Klotz John Srigley Michael A.S. Jewett David Mador Yves Fradet Jack Barkin Joseph Chin Jean-Marie Paquin Martin J. Bullock Suzanne Laplante 《The Journal of urology》1996,156(3):873-877
Purpose
A prospective, multicenter, randomized study was done to test the hypothesis that neoadjuvant androgen withdrawal decreases the incidence of positive margins following radical prostatectomy for localized prostate cancer.Materials and Methods
Observations were made of 213 patients randomized to undergo radical prostatectomy alone (101) or to receive a 12-week course of 300 mg. cyproterone acetate daily followed by surgery (112). Groups were similar at baseline in terms of clinical stage, serum prostate specific antigen and Gleason score. Of 192 patients available for efficacy analysis 9 had stage T1b, 8 stage T1c, 63 stage T2a, 36 stage T2b and 76 stage T2c disease.Results
One or more positive surgical margins were found in 59 of 91 patients (64.8 percent) in the surgery only group compared to 28 of 101 (27.7 percent) in the cyproterone acetate group (p = 0.001). Patients who received preoperative therapy had a statistically significantly lower rate of apical margin involvement than those who did not (17.8 versus 47.8 percent, respectively, p less than 0.0001). There was no statistically significant difference in surgical (p = 0.8645) or postoperative (p = 0.173) complications between the 2 groups.Conclusions
Neoadjuvant androgen withdrawal with a 12-week course of 300 mg. cyproterone acetate daily results in a lower rate of positive margins without adversely affecting postoperative recovery. The impact on patient survival will be determined by long-term followup. 相似文献29.
Human high molecular weight kininogen (HMWK), a single-chain protein with mol wt 120,000, is cleaved by human urinary kallikrein (HUK) to release kinin from within a disulfide loop and form a two-chain protein that retains all the procoagulant activity of the native molecule. Cleavage of HMWK by HUK is associated with a reduction in size to mol wt 115,000, as assessed by SDS-PAGE of unreduced protein, whereas the two chains of the reduced protein present together as a single broad band with mol wt 64,000. The 64,000 chain with procoagulant activity was chromatographically separated from the nonfunctional chain of similar size. The homogeneous procoagulant chain had an amino acid composition similar to that of smaller procoagulant ("light") chains isolated by others upon cleavage of HMWK with plasma kallikrein and elicited an antiserum that was monospecific by Ouchterlony analysis and inhibited the procoagulant function of HMWK. Thus, the limited proteolysis of HMWK by HUK has permitted, for the first time, the isolation of a stable procoagulant chain that is equal in size to the nonfunctional chain. The common terminology of "heavy" and "light" chain for kinin-free kininogen obtained with plasma kallikrein reflects the continued degradation of the procoagulant carboxyterminal chain and is not appropriate for the initial two-chain product formed when kinin is released from HMWK. It is proposed that the initial cleavage products of HMWK be designated the A-chain, the B-fragment, and the C- chain, representing the amino-terminal chain, the released vasoactive peptide containing the bradykinin sequence, and the carboxy-terminal procoagulant chain, respectively. Thus, intact HMWK would contain, in sequence, A, B, and C regions. 相似文献
30.
A. Heinz I. Suchy I. Klewin W. Kuhn P. Klotz H. Pruntek 《Journal of neural transmission (Vienna, Austria : 1996)》1992,4(4):291-301
Summary Twenty-nine patients with advanced Parkinson's disease were treated with subcutaneous lisuride infusion in addition to a basic therapy consisting of levodopa + PDI in all, and deprenyl in some patients. At the time of the report, 13 patients are still receiving lisuride infusion after 5–36 months, while 16 have dropped out after 0.5–30 months one because of psychosis, three because of insufficient efficacy, three due to death unrelated to treatment, three because of difficulties in handling the pump as outpatients, and six for other reasons. Off-periods and parkinsonian disability in off and in on were reduced significantly. These improvements remained constant throughout the observation period. Once the optimal dose regimen is established, only minor adjustments of the doses of lisuride and levodopa are required in the individual case. 相似文献