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61.
Zubrzycka M Janecka A 《Physiological research / Academia Scientiarum Bohemoslovaca》2008,57(5):769-776
Galanin (GAL) is suggested to be a neuropeptide involved in pain transmission. In this study we tried to determine, whether the increase of GAL concentration in brain cells affects impulse transmission between the motor centers localized in the vicinity of the third and fourth cerebral ventricles. The experiments were carried out on rats under chloralose anesthesia. The study objectives were realized using the method allowing to record the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation during the perfusion of the cerebral ventricles with solutions containing tested compounds. Perfusion of the cerebral ventricles with GAL concentration-dependently inhibited the ETJ amplitude. The antinociceptive effect of GAL was blocked by a galanin receptor antagonist, galantide (GLT) and by opioid antagonists: non-selective naloxone (Nal) and micro-selective beta-funaltrexamine (beta-FNA). In contrast, a delta-opioid receptor antagonist, naltrindole (NTI) or the kappa-opioid receptor antagonist, nor-binaltrophimine (nor-BNI) did not inhibit the effect of GAL. The antinociceptive effect of GAL was more pronounced when GAL was perfused in combination with other neuropeptides/neurohormones, such as endomorphin-2 (EM-2), vasopressin (AVP) and oxytocin (OT). The present results demonstrate that in the orofacial area analgesic activity is modulated by GAL, OT and AVP and that EM-2-induced antinociception involves GAL. 相似文献
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63.
Fichna J Perlikowska R Wyrębska A Gach K Piekielna J do-Rego JC Toth G Kluczyk A Janecki T Janecka A 《Bioorganic & medicinal chemistry》2011,19(23):6977-6981
This study reports the synthesis and biological evaluation of a series of new side-chain-to-side-chain cyclized endomorphin-2 (EM-2) and morphiceptin analogs of a general structure Tyr-c(Xaa-Phe-Phe-Yaa)NH(2) or Tyr-c(Xaa-Phe-D-Pro-Yaa)NH(2), respectively, where Xaa and Yaa were L/D Asp or L/D Lys. Further modification of these analogs was achieved by introduction of 2',6'-dimethyl-L-tyrosine (Dmt) instead of Tyr in position 1. Peptides were synthesized by solid phase method and cleaved from the resin by a microwave-assisted procedure. Dmt(1)-substituted analogs displayed high affinity at the μ-opioid receptors, remained intact after incubation with the rat brain homogenate and showed remarkable, long-lasting μ-opioid receptor-mediated antinociceptive activity after central, but not peripheral administration. Our results demonstrate that cyclization is a promising strategy in the development of new opioid analgesics, but further modifications are necessary to enhance the blood-brain barrier permeability. 相似文献
64.
Katarzyna Gach Anna Wyrębska Janusz Szemraj Anna Janecka 《Central European Journal of Biology》2012,7(3):411-418
Morphine, as well as opioid peptides, are well-known powerful analgesics. In addition to their use in the treatment of pain,
opioids appear to be important in the growth regulation of neoplastic tissue. However, little is known on the influence of
opioid peptides on apoptosis modulation in cancer cells. In the present study, we evaluated the effect of the μ-opioid receptor
(MOR)-selective peptide, morphiceptin and its two synthetic analogs, on mRNA expression and protein levels of some crucial
factors involved in apoptosis in three human cancer cell lines: MCF-7, HT-29, and SH-SY5Y. Using real-time PCR and ELISA assays,
we have shown that the selected opioid peptides enhanced apoptosis of cancer cells by increasing the expression of pro-apoptoticc
Bax and caspase-3, and decreasing expression of anti-apoptotic Bcl-2. Additionally, flow cytometry analysis performed on MCF-7
cells treated with annexin V/propidium iodide confirmed that the tested opioid peptides induced apoptosis in cancer cells.
However, induction of apoptosis was not reversed by the opioid antagonist, naloxone, which suggests that this process is not
mediated by the opioid receptors. 相似文献
65.
Renata Perlikowska Katarzyna Gach Jakub Fichna Geza Toth Bogdan Walkowiak Jean-Claude do-Rego Anna Janecka 《Bioorganic & medicinal chemistry》2009,17(11):3789-3794
Endogenous μ-opioid receptor (MOR) selective peptides, endomorphin-1 (EM-1) and endomorphin-2 (EM-2), unlike so called ‘typical opioids’, are characterized by the presence of Pro2 residue, which is a spacer connecting aromatic pharmacophoric residues. In order to investigate structural requirements for position 2, we synthesized endomorphin analogs incorporating, instead of Pro, unnatural amino acids with six-membered heterocyclic rings, such as piperidine 2-, 3- or 4-carboxylic acids (Pip, Nip and Inp, respectively). (R)-Nip residue turned out to be favourable for improving MOR affinity. Introduction of 2′,6′-dimethyltyrosine (Dmt) instead of Tyr1 led to obtaining [Dmt1, (R)-Nip2]EM-2 which showed exceptional MOR affinity and high stability against enzymatic degradation in rat brain homogenate. In in vivo hot-plate test in mice, this analog given intracerebroventicularly (i.c.v.), produced profound supraspinal analgesia, being much more potent than EM-2. The antinociceptive effect of this analog lasted about 170 min and was almost completely reversed by β-funaltrexamine (β-FNA), a selective MOR antagonist. 相似文献
66.
Poels J Nachman RJ Akerman KE Oonk HB Guerrero F De Loof A Janecka AE Torfs H Vanden Broeck J 《Peptides》2005,26(1):109-114
STKR is a neurokinin receptor derived from the stable fly, Stomoxys calcitrans. Insect tachykinin-related peptides, also referred to as "insectatachykinins", produce dose-dependent calcium and cyclic AMP responses in cultured Drosophila melanogaster Schneider 2 (S2) cells that were stably transfected with the cloned STKR cDNA. Pronounced differences in pharmacology were observed between agonist-induced calcium and cyclic AMP responses. The results indicate that the pharmacological properties of STKR depend on its coupling to a unique second messenger system. Therefore, a model postulating the existence of multiple active receptor conformations is proposed. This article presents the first evidence that an insect peptide receptor with dual coupling properties to second messenger systems can display agonist-dependent functional differences. 相似文献
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68.
Resolution of a concatenation/coalescence kerfuffle: partitioned coalescence support and a robust family‐level tree for Mammalia 下载免费PDF全文
John Gatesy Robert W. Meredith Jan E. Janecka Mark P. Simmons William J. Murphy Mark S. Springer 《Cladistics : the international journal of the Willi Hennig Society》2017,33(3):295-332
Recent phylogenetic analyses of a large dataset for mammalian families (169 taxa, 26 loci) portray contrasting results. Supermatrix (concatenation) methods support a generally robust tree with only a few inconsistently resolved polytomies, whereas MP‐EST coalescence analysis of the same dataset yields a weakly supported tree that conflicts with many traditionally recognized clades. Here, we evaluate this discrepancy via improved coalescence analyses with reference to the rich history of phylogenetic studies on mammals. This integration clearly demonstrates that both supermatrix and coalescence analyses of just 26 loci yield a congruent, well‐supported phylogenetic hypothesis for Mammalia. Discrepancies between published studies are explained by implementation of overly simple DNA substitution models, inadequate tree‐search routines and limitations of the MP‐EST method. We develop a simple measure, partitioned coalescence support (PCS), which summarizes the distribution of support and conflict among gene trees for a given clade. Extremely high PCS scores for outlier gene trees at two nodes in the mammalian tree indicate a troubling bias in the MP‐EST method. We conclude that in this age of phylogenomics, a solid understanding of systematics fundamentals, choice of valid methodology and a broad knowledge of a clade's taxonomic history are still required to yield coherent phylogenetic inferences. 相似文献
69.
W. Koziolkiewicz J. Pankowski A. Janecka 《Preparative biochemistry & biotechnology》2013,43(6):471-478
A new chemical method for the synthesis of adenosine 5′-γ-[32p] triphosphate has been developed based on the reaction of adenosine 5′- diphosphate with ethyl chloro-formate. The resulting active mixed anhydride was able to react with [32p]-triethylammonium orthophosphate to give γ-[32p]atp. 相似文献
70.
Fichna J do-Rego JC Costentin J Chung NN Schiller PW Kosson P Janecka A 《Biochemical and biophysical research communications》2004,320(2):531-536
Analogs of morphiceptin (Tyr-Pro-Phe-Pro-NH2), a mu-selective opioid receptor ligand, with position 3-modifications, including altered size, lipophilicity, and electronic character, while maintaining aromaticity were synthesized. The activity of the new analogs in in vitro assays and in in vivo hot-plate test of analgesia was compared and the results were consistent. [D-1-Nal3]Morphiceptin was the most potent analog of this series with a 26-fold increase in mu-opioid receptor affinity, a 15-fold potency increase in the GPI assay, and a significant potency increase in the hot-plate analgesic test, as compared with morphiceptin. [d-Qal3]Morphiceptin was found to be a weak antagonist in the GPI assay. 相似文献