The Experts below are selected from a list of 264 Experts worldwide ranked by ideXlab platform
Najam A. Sharif - One of the best experts on this subject based on the ideXlab platform.
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Pharmacological characterization of an FP prostaglandin receptor on rat vascular smooth muscle cells (A7r5) coupled to phosphoinositide turnover and intracellular Calcium Mobilization.
The Journal of pharmacology and experimental therapeutics, 1998Co-Authors: Brenda W. Griffin, Peggy E. Magnino, Iok-hou Pang, Najam A. SharifAbstract:An FP prostaglandin (PG) receptor on the A7r5 rat aorta smooth muscle cell line has been characterized by assays of phosphoinositide (PI) turnover and intracellular Calcium Mobilization stimulated by structurally diverse PGs. In the PI turnover assay, cloprostenol was the most potent PG tested, with a potency (EC50) of 0.84 ± 0.06 nM (mean ± S.E.M., n = 34), and was a full agonist. Other known FP receptor agonists tested in this assay had efficacies ≥85% of the cloprostenol value and high potencies: 16-phenoxy PGF2α (2.05 ± 0.19 nM), 17-phenyl PGF2α (2.80 ± 0.59 nM), fluprostenol (4.45 ± 0.19 nM), PGF2α (30.9 ± 2.82 nM) and PhXA85 (43.5 ± 11.4 nM). Other classes of PGs evaluated (PGD2, enprostil, 17-phenyl PGE2, PGE2, sulprostone and U-46619) were less potent and less efficacious than the FP receptor agonists, or were inactive. For a large group of standard PGs evaluated in the PI turnover assay, both potencies and efficacies correlated well with those reported for the FP receptor of Swiss mouse 3T3 fibroblasts. The potencies of fluprostenol and PGF2α as stimuli of intracellular Calcium Mobilization matched well their potencies in the PI turnover assay, but fluprostenol had twice the efficacy of PGF2α. Both signaling responses stimulated by fluprostenol were significantly inhibited by U73122, a selective inhibitor of phosphoinositide turnover (IC50 = 1.25 ± 0.16 μM for PI turnover), and by chelation of Calcium in the medium. Together with the PI turnover data, these studies of intracellular Calcium Mobilization linked to activation of the FP receptor, provide additional characterization of the pharmacological properties of this receptor.
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fp prostaglandin receptors mediating inositol phosphates generation and Calcium Mobilization in swiss 3t3 cells a pharmacological study
Journal of Pharmacology and Experimental Therapeutics, 1997Co-Authors: Brenda W. Griffin, Gary W Williams, Julie Y Crider, Najam A. SharifAbstract:A detailed pharmacological characterization of the prostaglandin (PG) receptor coupled to phosphoinositide (PI) turnover and intracellular Calcium Mobilization in Swiss 3T3 mouse fibroblast cells was undertaken. The pharmacological profile of this functional receptor was compared with the pharmacological profile of specific [3H]PGF2 α binding to bovine corpus luteum membranes, which are known to contain a bona fide FP receptor. PGs that were potent stimulators and full agonists in the PI turnover assay in the 3T3 cells were the following (for all, n = 3–45): 16-phenoxy-PGF2 α (EC50 = 0.61 ± 0.1 nM), cloprostenol (EC50 = 0.73 ± 0.04 nM), 17-phenyl-PGF2 α (EC50 = 2.71 ± 0.35 nM), fluprostenol (EC50 = 3.67 ± 0.61 nM), PhXA85 (EC50 = 27.3 ± 5.63 nM) and PGF2 α (EC50 = 28.5 ± 5.26 nM). However, PGD2 (EC50 = 155 ± 29.9 nM; E max = 49% of cloprostenol), PGE2 (EC50 = 2570 ± 566 nM; E max = 59%) and U46619 (EC50 = 1060 ± 310 nM; E max = 63%) were less potent and were partial agonists, and iloprost and BW245C were inactive. Although the PGs tested exhibited lower affinities in the [3H]PGF2 α binding assay than their functional potencies in the PI turnover assay, the rank orders of potencies and affinities were well correlated ( r = 0.94; n = 15 compounds). However, the PI turnover assay was more sensitive than the Calcium Mobilization assay for rank ordering PG agonists. In conclusion, the Swiss 3T3 cells express an FP receptor coupled to PI turnover and intracellular Ca++Mobilization signal transduction pathways. The pharmacological profile of this receptor was similar to that of the FP receptor found in the bovine corpus luteum, a tissue previously used to clone the first pharmacologically defined FP receptor.
Brenda W. Griffin - One of the best experts on this subject based on the ideXlab platform.
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Pharmacological characterization of an FP prostaglandin receptor on rat vascular smooth muscle cells (A7r5) coupled to phosphoinositide turnover and intracellular Calcium Mobilization.
The Journal of pharmacology and experimental therapeutics, 1998Co-Authors: Brenda W. Griffin, Peggy E. Magnino, Iok-hou Pang, Najam A. SharifAbstract:An FP prostaglandin (PG) receptor on the A7r5 rat aorta smooth muscle cell line has been characterized by assays of phosphoinositide (PI) turnover and intracellular Calcium Mobilization stimulated by structurally diverse PGs. In the PI turnover assay, cloprostenol was the most potent PG tested, with a potency (EC50) of 0.84 ± 0.06 nM (mean ± S.E.M., n = 34), and was a full agonist. Other known FP receptor agonists tested in this assay had efficacies ≥85% of the cloprostenol value and high potencies: 16-phenoxy PGF2α (2.05 ± 0.19 nM), 17-phenyl PGF2α (2.80 ± 0.59 nM), fluprostenol (4.45 ± 0.19 nM), PGF2α (30.9 ± 2.82 nM) and PhXA85 (43.5 ± 11.4 nM). Other classes of PGs evaluated (PGD2, enprostil, 17-phenyl PGE2, PGE2, sulprostone and U-46619) were less potent and less efficacious than the FP receptor agonists, or were inactive. For a large group of standard PGs evaluated in the PI turnover assay, both potencies and efficacies correlated well with those reported for the FP receptor of Swiss mouse 3T3 fibroblasts. The potencies of fluprostenol and PGF2α as stimuli of intracellular Calcium Mobilization matched well their potencies in the PI turnover assay, but fluprostenol had twice the efficacy of PGF2α. Both signaling responses stimulated by fluprostenol were significantly inhibited by U73122, a selective inhibitor of phosphoinositide turnover (IC50 = 1.25 ± 0.16 μM for PI turnover), and by chelation of Calcium in the medium. Together with the PI turnover data, these studies of intracellular Calcium Mobilization linked to activation of the FP receptor, provide additional characterization of the pharmacological properties of this receptor.
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fp prostaglandin receptors mediating inositol phosphates generation and Calcium Mobilization in swiss 3t3 cells a pharmacological study
Journal of Pharmacology and Experimental Therapeutics, 1997Co-Authors: Brenda W. Griffin, Gary W Williams, Julie Y Crider, Najam A. SharifAbstract:A detailed pharmacological characterization of the prostaglandin (PG) receptor coupled to phosphoinositide (PI) turnover and intracellular Calcium Mobilization in Swiss 3T3 mouse fibroblast cells was undertaken. The pharmacological profile of this functional receptor was compared with the pharmacological profile of specific [3H]PGF2 α binding to bovine corpus luteum membranes, which are known to contain a bona fide FP receptor. PGs that were potent stimulators and full agonists in the PI turnover assay in the 3T3 cells were the following (for all, n = 3–45): 16-phenoxy-PGF2 α (EC50 = 0.61 ± 0.1 nM), cloprostenol (EC50 = 0.73 ± 0.04 nM), 17-phenyl-PGF2 α (EC50 = 2.71 ± 0.35 nM), fluprostenol (EC50 = 3.67 ± 0.61 nM), PhXA85 (EC50 = 27.3 ± 5.63 nM) and PGF2 α (EC50 = 28.5 ± 5.26 nM). However, PGD2 (EC50 = 155 ± 29.9 nM; E max = 49% of cloprostenol), PGE2 (EC50 = 2570 ± 566 nM; E max = 59%) and U46619 (EC50 = 1060 ± 310 nM; E max = 63%) were less potent and were partial agonists, and iloprost and BW245C were inactive. Although the PGs tested exhibited lower affinities in the [3H]PGF2 α binding assay than their functional potencies in the PI turnover assay, the rank orders of potencies and affinities were well correlated ( r = 0.94; n = 15 compounds). However, the PI turnover assay was more sensitive than the Calcium Mobilization assay for rank ordering PG agonists. In conclusion, the Swiss 3T3 cells express an FP receptor coupled to PI turnover and intracellular Ca++Mobilization signal transduction pathways. The pharmacological profile of this receptor was similar to that of the FP receptor found in the bovine corpus luteum, a tissue previously used to clone the first pharmacologically defined FP receptor.
G N Burrow - One of the best experts on this subject based on the ideXlab platform.
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Control of thyroid secretion: effects of stimulators of protein kinase C, thyrotropin, and Calcium Mobilization on secretion of iodinated compounds from sheep thyroid cells.
Endocrinology, 1992Co-Authors: Margaret C. Eggo, H Lippes, G N BurrowAbstract:We have compared and contrasted the abilities of TSH and agents capable of discretely activating the cAMP-dependent protein kinase, protein kinase C, or Calcium Mobilization to influence the secretion of iodinated compounds from cells prelabeled with iodide and blocked from further organification with methimazole. We found that Calcium Mobilization induced by A23187, protein kinase C activation induced by 12-O-tetradecanoyl phorbol 13-acetate (TPA) and TSH all stimulated the secretion of iodinated compounds. The effects of TSH were mimicked by forskolin and those of TPA by a synthetic diacylglycerol, sn-1,2-dioctanoylglycerol. The effects of TPA were partially inhibited by staurosporine whereas those of TSH were not. Epidermal growth factor and norepinephrine were without effect on thyroid secretion. The effects of A23187 and TPA were synergistic. The effects of TSH and TPA were not and the increased secretion induced by either agent was partially prevented by the combination. Preincubation of cells with ...
Tadashi Yamamoto - One of the best experts on this subject based on the ideXlab platform.
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bank regulates bcr induced Calcium Mobilization by promoting tyrosine phosphorylation of ip3 receptor
The EMBO Journal, 2002Co-Authors: Kazumasa Yokoyama, Tohru Tezuka, Tomoharu Yasuda, Katsuhiko Mikoshiba, Alexander Tarakhovsky, Tadashi YamamotoAbstract:B-cell activation mediated through the antigen receptor is dependent on activation of protein tyrosine kinases (PTKs) such as Lyn and Syk and subsequent phosphorylation of various signaling proteins. Here we report on the identification and characterization of the B-cell scaffold protein with ankyrin repeats (BANK), a novel substrate of tyrosine kinases. BANK is expressed in B cells and is tyrosine phosphorylated upon B-cell antigen receptor (BCR) stimulation, which is mediated predominantly by Syk. Overexpres sion of BANK in B cells leads to enhancement of BCR-induced Calcium Mobilization. We found that both Lyn and inositol 1,4,5-trisphosphate receptor (IP(3)R) associate with the distinct regions of BANK and that BANK promotes Lyn-mediated tyrosine phosphorylation of IP(3)R. Given that IP(3)R channel activity is up-regulated by its tyrosine phosphorylation, BANK appears to be a novel scaffold protein regulating BCR-induced Calcium Mobilization by connecting PTKs to IP(3)R. Because BANK expression is confined to functional BCR-expressing B cells, BANK-mediated Calcium Mobilization may be specific to foreign antigen-induced immune responses rather than to signaling required for B-cell development.
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BANK regulates BCR-induced Calcium Mobilization by promoting tyrosine phosphorylation of IP(3) receptor.
The EMBO journal, 2002Co-Authors: Kazumasa Yokoyama, Tohru Tezuka, Tomoharu Yasuda, Katsuhiko Mikoshiba, Alexander Tarakhovsky, Tadashi YamamotoAbstract:B-cell activation mediated through the antigen receptor is dependent on activation of protein tyrosine kinases (PTKs) such as Lyn and Syk and subsequent phosphorylation of various signaling proteins. Here we report on the identification and characterization of the B-cell scaffold protein with ankyrin repeats (BANK), a novel substrate of tyrosine kinases. BANK is expressed in B cells and is tyrosine phosphorylated upon B-cell antigen receptor (BCR) stimulation, which is mediated predominantly by Syk. Overexpres sion of BANK in B cells leads to enhancement of BCR-induced Calcium Mobilization. We found that both Lyn and inositol 1,4,5-trisphosphate receptor (IP(3)R) associate with the distinct regions of BANK and that BANK promotes Lyn-mediated tyrosine phosphorylation of IP(3)R. Given that IP(3)R channel activity is up-regulated by its tyrosine phosphorylation, BANK appears to be a novel scaffold protein regulating BCR-induced Calcium Mobilization by connecting PTKs to IP(3)R. Because BANK expression is confined to functional BCR-expressing B cells, BANK-mediated Calcium Mobilization may be specific to foreign antigen-induced immune responses rather than to signaling required for B-cell development.
Robert A. Furilla - One of the best experts on this subject based on the ideXlab platform.
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Inhibition of smooth muscle cell Calcium Mobilization and aortic ring contraction by lactone vastatins.
Journal of hypertension, 1996Co-Authors: Nelson Escobales, Maria J. Crespo, Pablo I. Altieri, Robert A. FurillaAbstract:To determine the effects of vastatins on the contraction of rat aortic rings and to assess their effects on Calcium Mobilization using cultured smooth muscle cells from rat aorta. Aortic rings from Sprague-Dawley rats were mounted on stainless steel wires to determine the generation of tension using force-displacement transducers. The tension (g) developed by angiotensin II (100 nmol/l) was measured under basal conditions and after 45 min incubation with 20 micromol/l simvastatin. The effect of 20 mol/l simvastatin, lovastatin, mevastatin and pravastatin on noradrenaline concentration-response curves and the angiotensin II-induced Calcium Mobilization was also evaluated. Addition of angiotensin II to aortic rings incubated in Krebs' Ringer bicarbonate medium produced tension generation (0.9 +/- 0.12 g = 100%). Treatment of aortic rings with simvastatin inhibited the angiotensin II-induced contraction 58 +/- 0.06%. To evaluate this effect further, dose-response curves with noradrenaline were measured in the presence and absence of 20 micromol/l simvastatin, lovastatin, mevastatin and pravastatin. The results indicate that simvastatin, lovastatin and mevastatin inhibited the contraction induced by noradrenaline (10 micromol/l) by about 50%. Pravastatin did not inhibit aortic ring contraction. Furthermore, the concentration required for 50% of the maximal contraction (EC50) by noradrenaline (6.2 +/- 0.1 nmol/l) was significantly increased by simvastatin, lovastatin, mevastatin and pravastatin. The inhibition of vascular contraction by vastatins appears to involve inhibition of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity because the inhibitory effect of simvastatin was reduced 50% by 10 mmol/l mevalonic acid. To determine whether the depression of vascular contraction by these agents was correlated with cell Calcium changes, the angiotensin II-induced Calcium Mobilization was determined in Fura-2 loaded cells, before and after treatment with these inhibitors. Simvastatin, lovastatin and mevastatin significantly reduced the angiotensin II-induced Calcium Mobilization. The concentration that induced 50% inhibition was 3.3 micromol/l for simvastatin, 17.4 micromol/l for mevastatin and 21.7 micromol/l for lovastatin. No effect of pravastatin on Calcium Mobilization was observed. These findings suggest that lactone vastatins depress vascular contraction by reducing cytosolic Calcium release in vascular smooth muscle cells. These agents also appear to exert competitive and non-competitive type antagonisms on noradrenaline action.
