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排序方式: 共有348条查询结果,搜索用时 24 毫秒
31.
Valeria Camarda Carmela Fischetti Nicholas Anzellotti Paola Molinari Caterina Ambrosio Evi Kostenis Domenico Regoli Claudio Trapella Remo Guerrini Salvadori Severo Girolamo Calo 《Naunyn-Schmiedeberg's archives of pharmacology》2009,379(6):599-607
In this study, the Gαqi5 protein was used to force the human nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor to signal through the Ca2+ pathway in CHO cells. [Ca2+]i levels were monitored using the fluorometer FlexStation II and the Ca2+ dye Fluo 4 AM. Concentration response curves were generated with a panel of full and partial agonists, while NOP antagonists
were assessed in inhibition-response curves. The following rank order of potency of antagonists was measured: naloxone, which is superimposable to literature findings. The rank order of potency of full and partial agonists is also
similar to that obtained in previous studies with the exception of a panel of ligands (UFP-112, Ro 64-6198, ZP120, UFP-113)
whose potency was relatively low in the Gαqi5–NOP receptor calcium assay. Interestingly, these NOP ligands are characterized by slow kinetic of interaction with the NOP
receptor, as demonstrated by bioassay experiments. These results demonstrated that the FlexStation II–Gαqi5–NOP receptor calcium assay represents an adequate and useful screening for NOP receptor ligands, particularly for antagonists. 相似文献
32.
Mangiavacchi M Gasparini M Genovese S Pini D Klersy C Bragato R Andreuzzi B Municinò A Regoli F Galimberti P Ceriotti C Gronda E 《Pacing and clinical electrophysiology : PACE》2008,31(11):1425-1432
Background: Cardiac resynchronization therapy (CRT) improves cardiac performance and survival in patients with congestive heart failure. Recent observations suggest that diabetes is associated with a worse outcome in these patients. The aim of the study was to investigate the effect of diabetes and insulin treatment on outcome after CRT. Methods: Diabetic status and insulin treatment were assessed in 447 patients who underwent CRT (males 80.8%, mean age 65.7 ± 9.7 years, ejection fraction 29.9 ± 6.11%). Patients were stratified in three groups according to the presence or absence of diabetes and insulin treatment. Results: Nondiabetic patients were 366 (79.6%), noninsulin‐treated diabetic patients 62 (13.9%), insulin‐treated diabetic patients 29 (6.5%). The estimated death rate was 5.15 per 100 patients‐year in the nondiabetic group, 8.63 in noninsulin‐treated diabetics (HR 1.59, P = 0.240), and 15.84 in insulin‐treated diabetics (HR 3.05, P = 0.004). Cardiac mortality accounted for 81% of deaths in nondiabetic patients and for 56% of deaths in diabetic patients. Diabetic patients tended to have a worse recovery of left ventricular ejection fraction over time (P = 0.057) and of the distance at 6‐minute walking test (6MWT) (P = 0.018). Conclusions: Insulin‐treated diabetes is associated with a worse functional recovery and a higher mortality in patients with advanced heart failure after CRT. While cardiac death accounts for the majority of deaths in nondiabetic patients, a relevant proportion of the mortality in diabetic patients seem to result from noncardiac causes. 相似文献
33.
Conformation-activity relationship of neuropeptide S and some structural mutants: helicity affects their interaction with the receptor 总被引:1,自引:0,他引:1
Tancredi T Guerrini R Marzola E Trapella C Calo G Regoli D Reinscheid RK Camarda V Salvadori S Temussi PA 《Journal of medicinal chemistry》2007,50(18):4501-4508
Neuropeptide S (NPS) is the endogenous ligand of the previously orphan G-protein coupled receptor now named NPSR. The NPS-NPSR receptor system regulates important biological functions such as sleep/waking, locomotion, anxiety and food intake. Recently, exhaustive Ala scan and d-amino acid scan studies, together with systematic N- and C-terminal truncation, led to the identification of key residues for biological activity. Because conformational preferences might also play an important role, we undertook a detailed conformational analysis of NPS and several analogues in solution. We show that helicity induced by substitution of three flexible residues in the 5-13 regulatory region abolishes biological activity. A parallel pharmacological and conformational study of single and multiple substitutions of glycines 5, 7, and 9 showed that helicity can be tolerated in the C-terminal part of the peptide but not around Gly7. The identification of hNPSR partial agonists heralds the possibility of designing pure NPS receptor antagonists. 相似文献
34.
Christine Tousignant Gaetan Guillemette Guy Drapeau Sabine Telemaque Stephane Dion Domenico Regoli 《Brain research》1990,524(2)
The selective agonist [Sar9,Met(O2)11]-SP was radioiodinated with125I-Bolton Hunter in order to study its binding to rat brain membranes and for further comparison with125I-BH.SP. Specific binding of125I-BH[Sar9,Met(O211]-SP was temperature-dependent, saturable and reversible. In brain homogenates,125I-BH[Sar9,Met(O2)11]-SP interacted with a single class of high affinitykd = 1.0nM) non-interacting binding sites (Bmax of 15 fmol/mg protein). In the central nervous system,125I-BH-[Sar9,Met(O2)11]-SP apparently labeled the same number of binding sites as125I-BH.SP (19 fmol/mg protein). Competition studies with tachykinins, neurokinins and selective neurokinin agonists indicated that the pharmacological profile of the site labeled by125I-BH[Sar9,Met(O211]-SP is identical with that of NK-1 receptors. In dose-displacement studies made with radiolabeled SP and [Sar9,Met(O211)]-SP, an excellent correlation (r = 0.96) was found for theKi values of the different compounds tested; these findings suggest that both radioligands recognize the same receptor in rat brain. The affinity (Ki of various neurokinin-related peptides for the brain site were compared with their biological activities on various isolated organs (dog carotid artery, guinea-pig ileum, rat portal vein). NK-1 binding sites characterized in rat brain homogenates appear to be identical with those present on the dog carotid artery, a preparation known to possess exclusively the NK-1 receptor type. 相似文献
35.
A series of 15–18 compounds that act on NK1 or NK2 receptors as agonists or antagonists have been tested in the monoreceptor systems of the rabbit vena cava (NK1) and the rabbit pulmonary artery (NK2) for biological activities and for their ability to displace [3H] [Sar9, Met(O2)11]SP or [125I] NKA respectively from NK1 or NK2 human binding sites obtained by transfection and functional expression of the cDNAs for these receptor subtypes in CHO-K1 cells. For the two tachykinin receptors studied, positive highly significant correlations have been shown between binding and biological assays. Slopes of correlations are linear and near unity (r = 0.918 and 0.938). For NK1 and NK2 receptors the pharmacology in human and rabbit tissues appears to be very similar. The assays of biological activity on rabbit tissues may be therefore used to complement binding studies on human transfected cells to identify new antagonists for human tachykinin receptors. 相似文献
36.
Notti A Fattorini D Razzetti EM Regoli F 《Environmental toxicology and chemistry / SETAC》2007,26(6):1186-1191
The Mediterranean fan worm Sabella spallanzanii is characterized by elevated basal levels of arsenic in branchial crowns (>1000 microg/g) and an unusual prevalence of dimethylarsinic acid (DMA), a relatively toxic compound with a possible antipredatory role. The aim of this work was to obtain further insights on the capability of this polychaete to accumulate arsenic from different compounds and to operate biotransformation reactions. Laboratory exposures to arsenate (As(V)), dimethylarsinic acid (DMA), trimethylarsine (TMA), and arsenobetaine (AsB) revealed significant differences among tissues and kind of experiments. The highest increases of arsenic content were observed in branchial crowns of organisms treated with arsenate, which can enter the cell through the phosphate carrier system; lower variations were measured with DMA and TMA, while not-significant changes of total As occurred after treatments with AsB. In body tissues, exposure to As(V), DMA, and TMA confirmed a progressively lower accumulation of total arsenic, while a marked increase was caused by AsB. Obtained results suggested that accumulated arsenic could be chemically transformed, thus explaining the elevated basal levels of DMA typical of S. spallanzanii; during all the experiments, DMA was the most accumulated molecule, suggesting that this species possesses the enzymatic pathways for methylation and demethylation reactions of inorganic and trimethylated arsenicals. Only arsenobetaine was not converted into DMA, which would confirm a microbial pathway for degradation for this molecule, particularly important in body tissues of S. spallanzanii for the presence of bacteria associated to digestive tracts. Overall, the present study suggests future investigations on the biological role of arsenic and DMA in S. spallanzanii as a potential adaptive mechanism against predation in more vulnerable tissues. 相似文献
37.
Characterization of neurokinin effects and receptor selectivity in human isolated bronchi 总被引:7,自引:0,他引:7
E Naline P Devillier G Drapeau L Toty H Bakdach D Regoli C Advenier 《The American review of respiratory disease》1989,140(3):679-686
Sensitive afferent nerves and the neurokinins they release upon activation are considered to be important in controlling bronchomotor tone. Human isolated bronchi respond to neurokinin A (NKA), substance P (SP), and neurokinin B (NKB) with dose-dependent contractions. The order of potency of the three natural neurokinins is NKA greater than SP greater than NKB, suggesting the presence of NK-2 receptors. To further characterize the neurokinin receptors in human bronchi, we used selective agonists for each receptor type (i.e., NK-1, NK-2, and NK-3). In fact, NK-1 selective compounds, [Pro9]SP(1-11) sulfone and [beta-ala4,Sar9]SP(4-11) sulfone, did not induce significant contractions up to 10(-5) M. Similarly, the selective agonist for the NK-3 receptor, [MePhe7]NKB(4-10), was almost inactive. However, the NK-2 selective fragment [Nle]NKA(4-10) was a potent stimulant. The negative log of the peptide concentration that caused 50% of maximal effect (pD2) was 6.99 for NKA and 6.12 for [Nle10]NKA(4-10). Removal of the epithelium significantly enhanced the contractile responses to the three neurokinins and also to the NK-2 selective agonist. Phosphoramidon, an enkephalinase inhibitor, was more potent than epithelium removal in enhancing the contractile responses to these agonists. However, epithelium removal and phosphoramidon did not increase the weak responses to the NK-1 and NK-3 selective compounds. In the presence of phosphoramidon, removal of the epithelium slightly enhanced the contractile responses to NKA and [Nle]NKA(4-10) but not to SP and NKB.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
38.
Cecilia Fantoni Santi Raffa Francois Regoli Francesco Giraldi Maria Teresa La Rovere John Prentice Francesca Pastori Simona Fratini Jorge A Salerno-Uriarte Helmut U Klein Angelo Auricchio 《Journal of the American College of Cardiology》2005,46(10):1875-1882
OBJECTIVES: This study sought to report long-term changes of cardiac autonomic control by continuous, device-based monitoring of the standard deviation of the averages of intrinsic intervals in the 288 five-min segments of a day (SDANN) and of heart rate (HR) profile in heart failure (HF) patients treated with cardiac resynchronization therapy (CRT). BACKGROUND: Data on long-term changes of time-domain parameters of heart rate variability (HRV) and of HR in highly symptomatic HF patients treated with CRT are lacking. METHODS: Stored data were retrieved for 113 HF patients (New York Heart Association functional class III to IV, left ventricular ejection fraction < or =35%, QRS >120 ms) receiving a CRT device capable of continuous assessment of HRV and HR profile. RESULTS: The CRT induced a reduction of minimum HR (from 63 +/- 9 beats/min to 58 +/- 7 beats/min, p < 0.001) and mean HR (from 76 +/- 10 beats/min to 72 +/- 8 beats/min, p < 0.01) and an increase of SDANN (from 69 +/- 23 ms to 93 +/- 27 ms, p < 0.001) at three-month follow-up, which were consistent with improvement of functional capacity and structural changes. Different kinetics were observed among these parameters. The SDANN reached the plateau before minimum HR, and mean HR was the slowest parameter to change. Suboptimal left ventricular lead position was associated with no significant functional and structural improvement as well as no change or even worsening of HRV. The two-year event-free survival rate was significantly lower (62% vs. 94%, p < 0.005) in patients without any SDANN change (Delta change < or =0%) compared with patients who showed an increase in SDANN (Delta change >0%) four weeks after CRT initiation. CONCLUSIONS: Cardiac resynchronization therapy is able to significantly modify the sympathetic-parasympathetic interaction to the heart, as defined by HR profile and HRV. Lack of HRV improvement four weeks after CRT identifies patients at higher risk for major cardiovascular events. 相似文献
39.
Interaction of tachykinins with their receptors studied with cyclic analogues of substance P and neurokinin B. 总被引:1,自引:0,他引:1
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O Ploux S Lavielle G Chassaing S Julien A Marquet P d'Orlans-Juste S Dion D Regoli J C Beaujouan L Bergstrm et al. 《Proceedings of the National Academy of Sciences of the United States of America》1987,84(22):8095-8099
The activities of two groups of cyclic agonists of substance P (SP) have been studied. The disulfide bridge constraints have been designed on the basis of conformational studies on SP and physalaemin indicating an alpha-helical structure for the core of these two tachykinins (group I) and a folding of the C-terminal carboxamide towards the side chains of the glutamines 5 and 6 (group II). Only peptides simulating the alpha-helix present substantial potencies. [Cys3,6]SP is as active as SP in inhibiting 125I-labeled Bolton and Hunter SP-specific binding on rat brain synaptosomes and on dog carotid bioassay, two assays specific for the neurokinin 1 receptor. Moreover, [Cys3,6]SP is as potent as neurokinin B in inhibiting 125I-labeled Bolton and Hunter eledoisin-specific binding on rat cortical synaptosomes as well as in stimulating rat portal vein, two tests specific for the neurokinin 3 receptor. Interestingly, in contrast to neurokinin B, [Cys3,6]SP is a weak agonist of the neurokinin 2 receptor subtype, as evidenced by its binding potency in inhibiting 3H-labeled neurokinin A-specific binding on rat duodenum and in inducing the contractions of the rabbit pulmonary artery, a neurokinin 2-type bioassay. To increase the specificity of the cyclic analogue [Cys3,6]SP positions 8 and 9 were modified. [Cys3,6, Tyr8, Ala9]SP is slightly less selective than SP for the neurokinin 1 receptor subtype. [Cys2,5]neurokinin B constitutes a selective cyclic agonist for the neurokinin 3 receptor. The very weak potencies of the peptides from group II indicate that a certain degree of flexibility in the C-terminal moiety is required. Collectively, these results suggest that the neurokinin 1 and neurokinin 3 tachykinin receptors may recognize a similar three-dimensional structure of the core of the tachykinins. Different orientations of the common C-terminal tripeptide may be related to the selectivity for the different receptor subtypes. 相似文献
40.