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831.
Gastric parietal cell secretory membrane contains PKA- and acid-activated Kir2.1 K+ channels 总被引:2,自引:0,他引:2
Malinowska DH Sherry AM Tewari KP Cuppoletti J 《American journal of physiology. Cell physiology》2004,286(3):C495-C506
Our objective was to identify and localize a K+ channel involved in gastric HCl secretion at the parietal cell secretory membrane and to characterize and compare the functional properties of native and recombinant gastric K+ channels. RT-PCR showed that mRNA for Kir2.1 was abundant in rabbit gastric mucosa with lesser amounts of Kir4.1 and Kir7.1, relative to -actin. Kir2.1 mRNA was localized to parietal cells of rabbit gastric glands by in situ RT-PCR. Resting and stimulated gastric vesicles contained Kir2.1 by Western blot analysis at 50 kDa as observed with in vitro translation. Immunoconfocal microscopy showed that Kir2.1 was present in parietal cells, where it colocalized with H+-K+-ATPase and ClC-2 Cl- channels. Function of native K+ channels in rabbit resting and stimulated gastric mucosal vesicles was studied by reconstitution into planar lipid bilayers. Native gastric K+ channels exhibited a linear current-voltage relationship and a single-channel slope conductance of 11 pS in 400 mM K2SO4. Channel open probability (Po) in stimulated vesicles was high, and that of resting vesicles was low. Reduction of extracellular pH plus PKA treatment increased resting channel Po to 0.5 as measured in stimulated vesicles. Full-length rabbit Kir2.1 was cloned. When stably expressed in Chinese hamster ovary (CHO) cells, it was activated by reduced extracellular pH and forskolin/IBMX with no effects observed in nontransfected CHO cells. Cation selectivity was K+ = Rb+ >> Na+ = Cs+ = Li+ = NMDG+. These findings strongly suggest that the Kir2.1 K+ channel may be involved in regulated gastric acid secretion at the parietal cell secretory membrane. H+-K+-ATPase; hydrogen chloride secretion; parietal cell K+ channel 相似文献
832.
Juskowiak B Galezowska E Koczorowska N Hermann TW 《Bioorganic & medicinal chemistry letters》2004,14(14):3627-3630
The aggregation and DNA binding behavior of a new G-quadruplex selective ligand, 6a,12a-diazadibenzo-[a,g]fluorenylium derivative, was studied by UV-vis absorption and fluorescence spectroscopy. The formation of ligand aggregates with different spectral characteristics was observed at low and high concentration of NaCl, respectively. The ligand binds to G-quadruplex with much higher affinity than to single- and double-stranded DNA. 相似文献
833.
Drabczyńska A Müller CE Schumacher B Hinz S Karolak-Wojciechowska J Michalak B Pekala E Kieć-Kononowicz K 《Bioorganic & medicinal chemistry》2004,12(18):4895-4908
Synthesis and physicochemical properties of 7-mono- and 6,7-disubstituted dihydrooxazolo-[3,2-f]purinediones are described. Oxazolo[2,3-f]purinediones were synthesized by cyclization of 8-bromotheophylline with oxiranes. The obtained compounds (1-22) were evaluated for their affinity at adenosine A(1) and A(2A) receptors. They showed mainly adenosine A(2A) receptor affinity at low micromolar concentrations and A(2A) selectivity, for example, compound 9 with an octyl substituent at the oxazole ring displayed adenosine A(2A) receptor affinity (K(i)=0.998 microM) and at least 25-fold A(2A) versus A(1) selectivity. This compound was less selective (5-fold) towards human recombinant A(2B) and A(3) adenosine receptors. In this group of compounds active adenosine A(1) receptor antagonists were also identified. Oxazolopurinediones were evaluated in vivo as anticonvulsants in MES and ScMet tests and examined for neurotoxicity in mice (ip). Compounds with long alkyl chains showed anticonvulsant activity in both tests (in 100 and 300 mg/kg doses), accompanied by significant neurotoxicity. The anticonvulsant activity in rats (po) was higher and without signs of neurotoxicity. SAR and QSAR studies stressed the importance of lipophilic 7-substituents for both types of pharmacological activity. The volume of the substituent is, however, limited at the A(2A) AR, an n-octyl group being optimal. 相似文献
834.
Neural tube defects (NTDs) are a common cause of disability or death of new-borns, but the aetiology and genetic background of this disease are still poorly understood. Therefore, it was decided to determine the conditions for the identification of several polymorphisms and to perform a preliminary study on Polish NTD patients and their parents. According to the results of this study, the genetic predisposition to NTD can be correlated with the 677TT genotype in the MTHFR gene, 677CT/1298AC haplotype (the MTHFR gene), 2756G allele in the MTR gene, 66AG variant and minisatellite sequence with 5 or 10 repeats in intron 6 of the MTRR gene. The 530GG and TIVS7-2/TIVS7-2 genotypes in the T gene could also be considered as a risk factor for NTD. The analysis also revealed no correlation between neurulation disturbances and A4956G and A1186G mutations in the BRCA1 gene and the 844ins68bp in CBS gene. Although a correlation was found of some molecular markers with NTD, an additional examination should be conducted on more numerous groups to obtain statistically significant results. 相似文献
835.
Sherry AM Malinowska DH Morris RE Ciraolo GM Cuppoletti J 《American journal of physiology. Cell physiology》2001,280(6):C1599-C1606
HCl secretion across the parietal cell apical secretory membrane involves the H+-K+-ATPase, the ClC-2 Cl- channel, and a K+ channel. In the present study, the cellular and subcellular distribution of ClC-2 mRNA and protein was determined in the rabbit gastric mucosa and in isolated gastric glands. ClC-2 mRNA was localized to parietal cells by in situ hybridization and by direct in situ RT-PCR. By immunoperoxidase microscopy, ClC-2 protein was concentrated in parietal cells. Immunofluorescent confocal microscopy suggested that the ClC-2 was localized to the secretory canalicular membrane of stimulated parietal cells and to intracellular structures of resting parietal cells. Immunogold electron microscopy confirmed that ClC-2 is in the secretory canalicular membrane of stimulated cells and in tubulovesicles of resting parietal cells. These findings, together with previous functional characterization of the native and recombinant channel, strongly indicate that ClC-2 is the Cl- channel, which together with the H+-K+-ATPase and a K+ channel, results in HCl secretion across the parietal cell secretory membrane. 相似文献
836.
H Koz?owska E Schlicker M Koz?owski M Baranowska B Malinowska 《Journal of physiology and pharmacology》2006,57(3):317-328
The aim of our study was to examine whether non beta(1)-/beta(2)-adrenoceptors participate in the relaxation of the human pulmonary artery. For this purpose the vasodilatory effect of the non-conventional partial beta-adrenoceptor agonist cyanopindolol was examined. Cyanopindolol (1-300 microM), studied in the presence of the beta(1)-/beta(2)-adrenoceptor antagonist propranolol, relaxed the human pulmonary artery preconstricted with serotonin 1 microM in a concentration-dependent manner (maximally by about 80%). This effect was diminished by bupranolol 10 microM (an antagonist of beta(1)-beta(3)-adrenoceptors and the low affinity state of the beta(1)-adrenoceptor) and CGP 20712 10 microM (known to antagonize the low-affinity state of the beta(1)-adrenoceptor at high concentrations). In further experiments, the effect of beta-adrenoceptor ligands on the serotonin-induced vasoconstriction was examined. The concentration-response curve for serotonin was not affected by cyanopindolol 30 microM, bupranolol 10 microM and CGP 20712 10 microM but shifted to the right by cyanopindolol 100 and 300 microM; the serotonin 5-HT(2A) receptor antagonist ketanserin 0.3 microM abolished the maximum contraction elicited by serotonin. In conclusion, the present study reveals that the vasodilatory effect of cyanopindolol in the human pulmonary artery consists of two components, i.e. activation of a propranolol-insensitive atypical beta-adrenoceptor and antagonism against 5-HT(2A) receptors. 相似文献
837.
Pedro F. Teixeira Geoffrey Masuyer Catarina M. Pinho Rui M.M. Branca Beata Kmiec Cecilia Wallin Sebastian K.T.S. Wärmländer Ronnie P.-A. Berntsson Maria Ankarcrona Astrid Gräslund Janne Lehtiö Pål Stenmark Elzbieta Glaser 《Journal of molecular biology》2018,430(3):348-362
Proteolysis plays an important role in mitochondrial biogenesis, from the processing of newly imported precursor proteins to the degradation of mitochondrial targeting peptides. Disruption of peptide degradation activity in yeast, plant and mammalian mitochondria is known to have deleterious consequences for organism physiology, highlighting the important role of mitochondrial peptidases. In the present work, we show that the human mitochondrial peptidase neurolysin (hNLN) can degrade mitochondrial presequence peptides as well as other fragments up to 19 amino acids long. The crystal structure of hNLNE475Q in complex with the products of neurotensin cleavage at 2.7 Å revealed a closed conformation with an internal cavity that restricts substrate length and highlighted the mechanism of enzyme opening/closing that is necessary for substrate binding and catalytic activity. Analysis of peptide degradation in vitro showed that hNLN cooperates with presequence protease (PreP or PITRM1) in the degradation of long targeting peptides and amyloid-β peptide, Aβ1–40, associated with Alzheimer disease, particularly cleaving the hydrophobic fragment Aβ35–40. These findings suggest that a network of proteases may be required for complete degradation of peptides localized in mitochondria. 相似文献
838.
Thomas?SawidisEmail authorView authors OrcID profile
return OK on get Gülriz?Baycu Gül?Cevahir–?z Elzbieta?Weryszko-Chmielewska 《Protoplasma》2018,255(3):819-828
Pollen development and germination were adversely affected by the presence of mercury, whereas low-concentrations stimulated the whole procedure. Mercury caused morphological anomalies during the tube growth, characterized by irregularly increasing diameters and swelling tips. The main effect was the anomalous cell wall formation at the tip where a substantial number of organelles were found reducing the secretory vesicles. The dense organelle concentration caused a significant reduction of cytoplasmic movement integrity, and the cytosol streaming was gradually reduced or stopped completely. Electron dense, multilamellar myelin-like structures (MMS) of membranous material were frequently present, in close contact with plasmalemma or away from it. A loose network of fibrillar material and spherical aggregates mostly at the tip region were observed which progressively were loosened into the surrounding medium. Elevated mercury concentrations can affect plant reproduction, resulting in anomalies in gamete development and consequently loss of plant biodiversity. 相似文献
839.
Beata Sas-Korczynska Marian Reinfuss Jerzy W. Mitus Elzbieta Pluta Anna Patla Tomasz Walasek 《Reports of Practical Oncology and Radiotherapy》2018,23(5):402-406
Objectives
Radiotherapy in patients with sinonasal mucosal melanoma (SNMM) was given as alternative treatment to surgery in cases with advanced, inoperable tumors or those not eligible for surgery. We presented the outcomes for patients with SNMM treated with radiotherapy alone.Material and methods
The retrospective review of 6 consecutive SNMM (nasal cavity – 4 pts. and paranasal sinus – 2 pts.) patients (3 males and 3 females at mean age 64 years) treated between 2008 and 2016 was presented. The stage of disease was: T3 (1 pt.), T4a (3 pts.), T4b (2 pts.); with N0 and M0 in all patients. All patients underwent definitive primary photon radiotherapy (IMRT) alone; dose 66–72?Gy was delivered in 22–24 fractions given in 5 fractions (3?Gy) a week.Results
The complete remission was observed in all our patients but only one patient survived 5 years without disease. Five patients died due to multiple distant metastases; two of those patients developed associated local recurrence 7–8 months after radiotherapy.Conclusion
SNMM has a poor prognosis due to its high metastatic potential. Based on our numerically small report and data from literature we concluded that primary radiotherapy alone assured complete remission and even 5-year disease-free survival in only a few individual patients. 相似文献840.
Dariusz?L.?Szlachetko Elzbieta?Grochocka Magdalena?DudekEmail author Natalia?Ol?drzyńska 《Plant Systematics and Evolution》2018,304(2):231-243
Disperis tomaszii (Orchidaceae, Orchidoideae) from Cameroon is described and illustrated in this study. The new species is morphologically similar to Disperis nitida and Disperis thomensis. Phylogenetic analyses of selected DNA regions (ITS, matK) indicate a possible relationship between the new species and Disperis anthoceros and Disperis dicerochila. The taxonomic affinity between D. tomaszii and the aforementioned species is discussed. 相似文献