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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 352 (1995), S. 679-684 
    ISSN: 1432-1912
    Keywords: Key words Calmodulin antagonistsr ; Phosphoinositide turnover ; Phospholipase C ; C6-glioma cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To investigate the role of calmodulin (CaM)-dependent pathways in agonist-induced phosphoinositide (PI) turnover, the influence of several CaM antagonists on PI-phospholipase C (PLC) activation in intact and permeabilized C6 glioma cells was examined. The extent of PI turnover was assessed by measuring the accumulation of inositol phosphates (IPs) in the presence of LiCl in C6 glioma cells prelabelled with myo-[3H]inositol. Trifluoperazine, N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7), fendiline and calmidazolium themselves had no effect on basal IP formation, but concentration-dependently (1–30 μM) potentiated ATP-, NaF- and A23187-stimulated IP formation. The maximal response to ATP (1 mM) was increased by up to 50%, while the concentration for half-maximal effect (EC50, 60 μM) was unaffected by trifluoperazine. In digitonin-permeabilized C6 glioma cells, the concentration-dependent increase of PI-PLC activation elicited by free Ca2+ was potentiated by the GTP analogue, guanosine 5′-[γ-thio]triphosphate (GTPγS), with an EC50 of 6 μM. Trifluoperazine (1–30 μM) enhanced the Ca2+-stimulated IP formation concentration dependently and this potentiation was counteracted by the addition of CaM. In the combined presence of each CaM antagonist studied and GTPγS, an additive increase in IP formation was observed. The results indicate that CaM antagonists enhance stimulus-induced IP formation in C6 glioma cells primarily by increasing the Ca2+-dependent activation of PI-PLC.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 53-58 
    ISSN: 1432-1912
    Keywords: Key words SK&F 96365 ; M3 muscarinic receptor ; Phosphoinositide turnover ; SH-SY5Y neuroblastoma ; Cerebellar granule cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  SK&F 96365, a receptor-mediated Ca2+ entry inhibitor, has been reported to inhibit Ca2+ res- ponses to various agonists without affecting internal Ca2+ release and phosphoinositide turnover. Since muscarinic acetylcholine receptor-mediated phospho- inositide turnover shows a marked dependence on factors affecting cytosolic Ca2+ concentration, the effects of SK&F 96365 on the coupling of muscarinic receptors to the phosphoinositide hydrolysis were examined in human neuroblastoma SH-SY5Y and rat cerebellar granule cells. SK&F 96365 concentration-dependently (3–30 μM) inhibited the inositol phosphate formation elicited by carbachol in both cellular systems. Moreover, SK&F 96365 inhibited the carbachol-induced inositol phosphate formation in the absence of extracellular Ca2+, and similar extent of inhibition was achieved in the presence or absence of extracellular Ca2+. In ligand binding studies, we found that the binding affinities for [3H] N-methyl scopolamine in both cells were attenuated by SK&F 96365 (3–30 μM), while Bmax values for the ligand were not changed. The competition curves of SK&F 96365 showed a Ki value of 28.4 uM in SH-SY5Y cells. The results indicated that the decrease of carbachol-stimulated phosphoinositide hydrolysis by SK&F 96365 is due to the competitive inhibition of agonist binding to the M3 muscarinic receptors.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Clinical rheumatology 14 (1995), S. 441-444 
    ISSN: 1434-9949
    Keywords: Bone Scan ; Radiography ; Reiter's Disease ; Arthritis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tc-99m MDP bone scans were used to evaluate the articular inflammation in 38 patients with Reiter's disease and compared with clinical examination and radiologic findings. Our data showed that Reiter's disease predominantly involves the lower limbs, especially the heels, which may be a characteristic feature of Reiter's disease. Bone scans revealed a high diagnostic sensitivity in the detection of clinical arthritis in all peripheral joints, especially in the small joints of the four limbs. The diagnostic sensitivity of radiography was generally lower than bone scintigraphy. In the presence of positive radionuclide findings, clinical arthritis was found in most joints. The scintigram, however, detects a greater number of abnormalities than does clinical assessment in the sternoclavicular joints, shoulders, metacarpophalangeal joints, and tarsals. Because of its high sensitivity, bone scintigraphy is capable of detecting subclinical arthritis, and might provide more objective evidence of early inflammatory joint disease and additional information regarding the pattern of joint involvement. In view of the advantages of low patient radiation exposure, high sensitivity, and the ability to survey the whole body, we consider bone scintigraphy as useful and better than radiography in the detection of early articular inflammation and in establishing the extent and pattern of arthritis in Reiter's disease.
    Type of Medium: Electronic Resource
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