Effects of (-)-RO363 at human atrial beta-adrenoceptor subtypes, the human cloned beta(3)-adrenoceptor and rodent intestinal beta(3)-adrenoceptors

1 Chronic treatment of patients with beta-blockers causes atrial inotropic hyperresponsiveness through beta(2)-adrenoceptors, 5-HT4 receptors and H-2-receptors but apparently not through beta(1)-adrenoceptors despite data claiming an increased beta(1)-adrenoceptor density from homogenate binding studies. We have addressed the question of beta(1)-adrenoceptor sensitivity by determining the inotropic potency and intrinsic activity of the beta(1)-adrenoceptor selective partial agonist (-)-RO363 and by carrying out both homogenate binding and quantitative beta-adrenoceptor autoradiography in atria obtained from patients treated or not treated with beta-blockers. In the course of the experiments it became apparent that (-)-RO363 also may cause agonistic effects through the third atrial beta-adrenoceptor. To assess whether (-)-RO363 also caused agonistic effects through beta(3)-adrenoceptors we studied its relaxant effects in rat colon and guinea-pig ileum, as well as receptor binding and adenylyl cyclase stimulation of chinese hamster ovary (CHO) cells expressing human beta(3)-adrenoceptors. 2 beta-Adrenoceptors were labelled with (-)-[I-125]-cyanopindolol. The density of both beta(1)- and beta(2)-adrenoceptors was unchanged in the 2 groups, as assessed with both quantitative receptor autoradiography and homogenate binding. The affinities of (-)-RO363 for beta(1)-adrenoceptors (pK(i) = 8.0-7.7) and beta(2)-adrenoceptors (pK(i) = 6.1-5.8) were not significantly different in the two groups. 3 (-)-RO363 increased atrial force with a pEC(50) of 8.2 (beta-blocker treated) and 8.0 (non-beta-blocker treated) and intrinsic activity with respect to (-)-isoprenaline of 0.80 (beta-blocker treated) and 0.54 (non-beta-blocker treated) (P<0.001) and with respect to Ca2+ (7 mM) of 0.65 (beta-blocker treated) and 0.45 (non-beta-blocker treated) (P<0.01). The effects of (-)-RO363 were resistant to antagonism by the beta(2)-adrenoceptor antagonist, ICI 118,551 (50 nM). The effects of 0.3-10 nM (-)-RO363 were antagonized by 3-10 nM of the beta(1)-adrenoceptor selective antagonist CGP 20712A. The effects of 20-1000 nM (-)-RO363 were partially resistant to antagonism by 30-300 nM CGP 20712A. 4 (-)-RO363 relaxed the rat colon, partially precontracted by 30 mM KCl, with an intrinsic activity of 0.97 compared to (-)-isoprenaline. The concentration-effect curve to (-)-RO363 revealed 2 components, one antagonized by (-)-propranolol (200 nM) with pEC(50)=8.5 and fraction 0.66, the other resistant to (-)-propranolol (200 nM) with pEC(50)=5.6 and fraction 0.34 of maximal relaxation. 5 (-)-RO363 relaxed the longitudinal muscle of guinea-pig ileum, precontracted by 0.5 mu M histamine, with intrinsic activity of 1.0 compared to (-)-isoprenaline and through 2 components, one antagonized by (-)-propranolol (200 nM) with pEC(50)=8.7 and fraction 0.67, the other resistant to (-)-propranolol with pEC(50)=4.9 and fraction 0.33 of maximal relaxation. 6 (-)-RO363 stimulated the adenylyl cyclase of CHO cells expressing human beta(3)-adrenoceptors with pEC(50)=5.5 and intrinsic activity 0.74 with respect to (-)-isoprenaline (pEC(50)=5.9). (-)-RO363 competed for binding with [I-125]cyanopindolol at human beta(3)-adrenoceptors transfected into CHO cells with pK(i)=4.5. (-)-Isoprenaline (pk(i)=5.2) and (-)-CGP 12177A (pK(i)=6.1) also competed for binding at human beta(2)-adrenoceptors. 7 We conclude that under conditions used in this study, (-)-RO363 is a potent partial agonist for human beta(1)- and beta(3)-adrenoceptors and appears also to activate the third human atrial beta-adrenoceptor. (-)-RO363 relaxes mammalian gut through both beta(1)- and beta(3)-adrenoceptors. (-)-RO363, used as a beta(1)-adrenoceptor selective tool, confirms previous findings with (-)-noradrenaline that beta(1)-adrenoceptor mediated atrial effects are only slightly enhanced by chronic treatment of patients with beta-blockers. Chronic treatment with beta(1)-adrenoceptor-selective blockers does not significantly increase the density of human atrial beta(1)- and beta(2)-adrenoceptors.

1-Ethynyl-2-isopropoxy-3-methoxybenzene

The crystal structure of the title compound, C12H14O2, has been determined at 150 K. Significant intermolecular non-conventional C-H...O interactions involving the terminal acetylinic H atom are observed, which result in a zigzag hydrogen-bonded chain in the b direction.

Structural and magnetic studies of Schiff base complexes of nickel(ii) nitrite: change in crystalline state, ligand rearrangement and a very rare μ-nitrito-1κO:2κN:3κO′ bridging mode

Four new nickel(II) complexes, [Ni2L2(NO2)2]·CH2Cl2·C2H5OH, 2H2O (1), [Ni2L2(DMF)2(m-NO2)]ClO4·DMF (2a), [Ni2L2(DMF)2(m-NO2)]ClO4 (2b) and [Ni3L¢2(m3-NO2)2(CH2Cl2)]n·1.5H2O (3) where HL = 2-[(3-amino-propylimino)-methyl]-phenol, H2L¢ = 2-({3-[(2-hydroxy-benzylidene)-amino]-propylimino}-methyl)-phenol and DMF = N,N-dimethylformamide, have been synthesized starting with the precursor complex [NiL2]·2H2O, nickel(II) perchlorate and sodium nitrite and characterized structurally and magnetically. The structural analyses reveal that in all the complexes, NiII ions possess a distorted octahedral geometry. Complex 1 is a dinuclear di-m2-phenoxo bridged species in which nitrite ion acts as chelating co-ligand. Complexes 2a and 2b also consist of dinuclear entities, but in these two compounds a cis-(m-nitrito-1kO:2kN) bridge is present in addition to the di-m2-phenoxo bridge. The molecular structures of 2a and 2b are equivalent; they differ only in that 2a contains an additional solvated DMF molecule. Complex 3 is formed by ligand rearrangement and is a one-dimensional polymer in which double phenoxo as well as m-nitrito-1kO:2kN bridged trinuclear units are linked through a very rare m3-nitrito-1kO:2kN:3kO¢ bridge. Analysis of variable-temperature magnetic susceptibility data indicates that there is a global weak antiferromagnetic interaction between the nickel(II) ions in four complexes, with exchange parameters J of -5.26, -11.45, -10.66 and -5.99 cm-1 for 1, 2a, 2b and 3, respectively

Revisiting the addition reaction of TeCl4 to alkynes: the crystal structure and docking studies of 1-chloro-2-trichlorotelluro-3-phenyl-propen-2-ol

Tellurium tetrachloride adds to alkynes via two pathways: a concerted syn addition, that yields Z-tri- and tetra-substituted alkenes or by an anti addition that yields E-alkenes. The mechanistic aspects of these divergent pathways have been reevaluated at the light of crystallographic data. The molecules, of the title compound, in the crystal, are associated in a helical fashion with a Te...Te pitch of 6.3492(6) angstrom. As it exhibits inhibitory activity for cathepsin B and in order to gain more insight of the inhibition mechanism, a docking study was undertaken providing insight on why organic telluranes are more efficient inhibitors than inorganic ones as AS-101. (c) 2006 Elsevier B.V. All rights reserved.

Drei Gesänge aus dem "Hallel" : 1. Haudu ; 2. Ono ; 3. Boruch habo (für Trauungen)

für gemischten Chor componirt von Siegmund Rosenthal

Mus Hs 2645 - Pièces d'harmonie : tirés de l'opéra: Figaro & entre acts ; pour deux clarinettes, deux cors & deux bassons ; [parthie 1, parthie 2, parthie 3] ; [no. 6, 7 & 8]

arr. par Stumpf

Dinoflagellate cysts in surface sediment samples of METEOR cruises M20/2, M23/1, M34/1, M34/2, M34/3 and M34/4

To enhance the limited information available about the palaeo-ecological significance of calcareous dinoflagellates, we have studied their lateral distribution in surface sediments of the equatorial and south Atlantic between 13°N and 36°S. Calcareous dinoflagellate cysts appear to be widely distributed throughout the studied area. In the surface sediments, concentrations (cyst per gram dry sediment) of the vegetative stage Thoracosphaera heimii are generally higher than that of the (presumably) calcareous resting cysts. Distribution patterns in surface sediments of Orthopithonella granifera (Fütterer) Keupp and Versteegh, Rhabdothorax spp. Kamptner., Sphaerodinella albatrosiana (Kamptner) Keupp and Versteegh S. albatrosiana praratabulated, Sphaerodinella tuberosa var. 1 (Kamptner) Keupp and Versteegh and S. tuberosa var. 2 and the ratios between these species have been compared with temperature, salinity, density and stratification gradients in the upper water column. Rhabdothorax spp. is characteristically present in sediments of more temperate regions characterized by high seasonality. Dinoflagellates producing these cysts are able to tolerate high nutrient concentrations, and mixing of the water column. S. albatrosiana is abundant in regions characterized by high sea surface temperatures and oligotrophic surface water conditions. In contrast, the distribution of S. tuberosa var. 2 is negatively related to temperature. The other cyst species did not show a characteristic pattern in relation to the studied environmental gradients. The ratio of Sphaerodinella tuberosa var. 2 to Orthopithonella granifera can be used for reconstructing the presence of stratification in the upper 50 m of the water column, whereas the ratios of S. tuberosa var. 2 to Sphaerodinella albatrosiana and of O. granifera to Rhabdothorax spp. might be used for palaeotemperature reconstructions. Calcareous dinoflagellate cysts are abundant in oligotrophic areas and may be useful for the reconstruction of palaeoenvironmental conditions.

Ueber das 1-phenyl-2-propyl-3-methyl-5-pyrazolon.

Thesis (doctoral)--

Tidal rivers; their (1) hydraulics, (2) improvement, (3) navigation.

Mode of access: Internet.

Geological reference standards (JLK-1,JSD-1, JSD-2, JSD-3,JMS-1, JMS-2) measured by Itrax-XRF core scanner in different exposure times

X-ray fluorescence (XRF) core-scanning is a fast and nondestructive technique to assess elemental variations of unprocessed sediments. However, although the exposure time of XRF-scanning directly affects the scanning counts and total measurement time, only a few studies have considered the influence of exposure time during the scan. How to select an optimal exposure time to achieve reliable results and reduce the total measurement time is an important issue. To address this question, six geological reference materials from the Geological Survey of Japan (JLK-1, JMS-1, JMS-2, JSD-1, JSD-2, and JSD-3) were scanned by the Itrax-XRF core scanner using the Mo- and the Cr-tube with different exposure times to allow a comparison of scanning counts with absolute concentrations. The regression lines and correlation coefficients of elements that are generally used in paleoenvironmental studies were examined for the different exposure times and X-ray tubes. The results show that for those elements with relatively high concentrations or high detectability, the correlation coefficients are higher than 0.90 for all exposure times. In contrast, for the low detectability or low concentration elements, the correlation coefficients are relatively low, and improve little with increased exposure time. Therefore, we suggest that the influence of different exposure times is insignificant for the accuracy of the measurements. Thus, caution must be taken when interpreting the results of elements with low detectability, even when the exposure times are long and scanning counts are reasonably high.