The Experts below are selected from a list of 123 Experts worldwide ranked by ideXlab platform
Shuh Narumiya - One of the best experts on this subject based on the ideXlab platform.
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cloning and expression of cdna for a human thromboxane a2 Receptor
Nature, 1991Co-Authors: Masakazu Hirata, Yasunori Hayashi, Fumitaka Ushikubi, Yoshifumi Yokota, Ryoichiro Kageyama, Shigetada Nakanishi, Shuh NarumiyaAbstract:THROMBOXANE A2 is a very unstable arachidonate metabolite, yet a potent stimulator of platelet aggregation and a constrictor of vascular and respiratory smooth muscles1. It has been implicated as a mediator in diseases such as myocardial infarction, stroke and bronchial asthma2. Using a stable analogue of this compound we recently purified the human platelet thromboxane A2 Receptor to apparent homogeneity3. Using an oligonucleotide probe corresponding to its partial amino-acid sequence, we have obtained a complementary DNA clone encoding this Receptor from human placenta and a partial clone from cultured human megakaryocytic leukaemia cells. The placenta cDNA encodes a protein of 343 amino acids with seven putative transmembrane domains. The protein expressed in COS-7 cells binds drugs with affinities identical to those of the platelet Receptor, and that in Xenopus oocytes opens Ca2+-activated Cl- channel on agonist stimulation. Northern blot analysis and nucleotide sequences of the two clones suggest that an identical species of the thromboxane A2 Receptor is present in platelets and vascular tissues. This first report on the molecular structure of an Eicosanoid Receptor will promote the molecular pharmacology and pathophysiology of these bioactive compounds.
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Cloning and expression of cDNA for a human thromboxane A_2 Receptor
Nature, 1991Co-Authors: Masakazu Hirata, Yasunori Hayashi, Fumitaka Ushikubi, Yoshifumi Yokota, Ryoichiro Kageyama, Shigetada Nakanishi, Shuh NarumiyaAbstract:THROMBOXANE A_2 is a very unstable arachidonate metabolite, yet a potent stimulator of platelet aggregation and a constrictor of vascular and respiratory smooth muscles^1. It has been implicated as a mediator in diseases such as myocardial infarction, stroke and bronchial asthma^2. Using a stable analogue of this compound we recently purified the human platelet thromboxane A_2 Receptor to apparent homogeneity^3. Using an oligonucleotide probe corresponding to its partial amino-acid sequence, we have obtained a complementary DNA clone encoding this Receptor from human placenta and a partial clone from cultured human megakaryocytic leukaemia cells. The placenta cDNA encodes a protein of 343 amino acids with seven putative transmembrane domains. The protein expressed in COS-7 cells binds drugs with affinities identical to those of the platelet Receptor, and that in Xenopus oocytes opens Ca^2+-activated Cl^- channel on agonist stimulation. Northern blot analysis and nucleotide sequences of the two clones suggest that an identical species of the thromboxane A_2 Receptor is present in platelets and vascular tissues. This first report on the molecular structure of an Eicosanoid Receptor will promote the molecular pharmacology and pathophysiology of these bioactive compounds.
Masakazu Hirata - One of the best experts on this subject based on the ideXlab platform.
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cloning and expression of cdna for a human thromboxane a2 Receptor
Nature, 1991Co-Authors: Masakazu Hirata, Yasunori Hayashi, Fumitaka Ushikubi, Yoshifumi Yokota, Ryoichiro Kageyama, Shigetada Nakanishi, Shuh NarumiyaAbstract:THROMBOXANE A2 is a very unstable arachidonate metabolite, yet a potent stimulator of platelet aggregation and a constrictor of vascular and respiratory smooth muscles1. It has been implicated as a mediator in diseases such as myocardial infarction, stroke and bronchial asthma2. Using a stable analogue of this compound we recently purified the human platelet thromboxane A2 Receptor to apparent homogeneity3. Using an oligonucleotide probe corresponding to its partial amino-acid sequence, we have obtained a complementary DNA clone encoding this Receptor from human placenta and a partial clone from cultured human megakaryocytic leukaemia cells. The placenta cDNA encodes a protein of 343 amino acids with seven putative transmembrane domains. The protein expressed in COS-7 cells binds drugs with affinities identical to those of the platelet Receptor, and that in Xenopus oocytes opens Ca2+-activated Cl- channel on agonist stimulation. Northern blot analysis and nucleotide sequences of the two clones suggest that an identical species of the thromboxane A2 Receptor is present in platelets and vascular tissues. This first report on the molecular structure of an Eicosanoid Receptor will promote the molecular pharmacology and pathophysiology of these bioactive compounds.
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Cloning and expression of cDNA for a human thromboxane A_2 Receptor
Nature, 1991Co-Authors: Masakazu Hirata, Yasunori Hayashi, Fumitaka Ushikubi, Yoshifumi Yokota, Ryoichiro Kageyama, Shigetada Nakanishi, Shuh NarumiyaAbstract:THROMBOXANE A_2 is a very unstable arachidonate metabolite, yet a potent stimulator of platelet aggregation and a constrictor of vascular and respiratory smooth muscles^1. It has been implicated as a mediator in diseases such as myocardial infarction, stroke and bronchial asthma^2. Using a stable analogue of this compound we recently purified the human platelet thromboxane A_2 Receptor to apparent homogeneity^3. Using an oligonucleotide probe corresponding to its partial amino-acid sequence, we have obtained a complementary DNA clone encoding this Receptor from human placenta and a partial clone from cultured human megakaryocytic leukaemia cells. The placenta cDNA encodes a protein of 343 amino acids with seven putative transmembrane domains. The protein expressed in COS-7 cells binds drugs with affinities identical to those of the platelet Receptor, and that in Xenopus oocytes opens Ca^2+-activated Cl^- channel on agonist stimulation. Northern blot analysis and nucleotide sequences of the two clones suggest that an identical species of the thromboxane A_2 Receptor is present in platelets and vascular tissues. This first report on the molecular structure of an Eicosanoid Receptor will promote the molecular pharmacology and pathophysiology of these bioactive compounds.
Raymond N. Dubois - One of the best experts on this subject based on the ideXlab platform.
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Prostacyclin-mediated activation of peroxisome proliferator-activated Receptor δ in colorectal cancer
Proceedings of the National Academy of Sciences of the United States of America, 2000Co-Authors: Rajnish A. Gupta, Jian Tan, Wade F. Krause, Mark W. Geraci, Timothy M. Willson, Sudhansu K. Dey, Raymond N. DuboisAbstract:There is evidence from both genetic and pharmacologic studies to suggest that the cyclooxygenase-2 (COX-2) enzyme plays a causal role in the development of colorectal cancer. However, little is known about the identity or role of the Eicosanoid Receptor pathways activated by COX-derived prostaglandins (PG). We previously have reported that COX-2-derived prostacyclin promotes embryo implantation in the mouse uterus via activation of the nuclear hormone Receptor peroxisome proliferator-activated Receptor (PPAR) delta. In light of the recent finding that PPARdelta is a target of beta-catenin transactivation, it is important to determine whether this signaling pathway is operative during the development of colorectal cancer. Analysis of PPARdelta mRNA in matched normal and tumor samples revealed that expression of PPARdelta, similar to COX-2, is up-regulated in colorectal carcinomas. In situ hybridization studies demonstrate that PPARdelta is expressed in normal colon and localized to the epithelial cells at the very tips of the mucosal glands. In contrast, expression of PPARdelta mRNA in colorectal tumors was more widespread with increased levels in transformed epithelial cells. Analysis of PPARdelta and COX-2 mRNA in serial sections suggested they were colocalized to the same region within a tumor. Finally, transient transfection assays established that endogenously synthesized prostacyclin (PGI(2)) could serve as a ligand for PPARdelta. In addition, the stable PGI(2) analog, carbaprostacyclin, and a synthetic PPARdelta agonist induced transactivation of endogenous PPARdelta in human colon carcinoma cells. We conclude from these observations that PPARdelta, similar to COX-2, is aberrantly expressed in colorectal tumors and that endogenous PPARdelta is transcriptionally responsive to PGI(2). However, the functional consequence of PPARdelta activation in colon carcinogenesis still needs to be determined.
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The nuclear Eicosanoid Receptor, PPARgamma, is aberrantly expressed in colonic cancers.
Carcinogenesis, 1998Co-Authors: Raymond N. Dubois, Rajnish K. Gupta, Jeffrey A. Brockman, Bandaru S. Reddy, Samuel L. Krakow, Mitchell A. LazarAbstract:Continuous use of nonsteroidal anti-inflammatory drugs (NSAIDs) lowers the relative risk of colorectal cancer in humans and decreases tumor yield in rodents treated with carcinogens. One well documented target for NSAIDs is prostaglandin endoperoxide synthase (cyclooxygenase) and two isoforms of this enzyme have been identified, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). COX enzymes produce Eicosanoid products, some of which have recently been shown to activate transcription mediated by the nuclear hormone Receptor peroxisome proliferator activated Receptor gamma (PPARgamma), whose expression is largely restricted to adipose tissue. The present study was undertaken to determine if PPARgamma was expressed in colonic tumors. PPARgamma messenger RNA (mRNA) and protein levels were assayed in colonic tumors and normal adjacent mucosa, as well as in a variety of human colon cancer cell lines. There was a marked increase in PPARgamma RNA levels in four out of four of the colonic tumors compared to paired normal mucosa, where little expression of PPARgamma was detected. Western blotting analysis showed that PPARgamma protein was expressed in four out of five colonic tumor samples. PPARgamma was also expressed in a subset of polyps, and in certain human colon cancer cell lines as well. Additionally, we were able to demonstrate that an Eicosanoid, 15 deoxy-delta12,14 PGJ2, transactivated transcription of a PPRE-driven promoter in CaCo-2 cells. Thus, we have shown that PPARgamma gene and protein expression is elevated in rodent colon tumors, in selected human colon cancer cell lines and that the PPARgamma Receptor is functional in CaCo-2 cells. Since PPARgamma is a ligand-modulated transcription factor, it may provide a novel target for chemopreventive strategies for colorectal cancer.
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Introduction to Eicosanoids and the gastroenteric tract.
Gastroenterology clinics of North America, 1996Co-Authors: Raymond N. Dubois, Charles E. Eberhart, Christopher S. WilliamsAbstract:Eicosanoids are produced throughout the gastrointestinal tract and are significant mediators of physiologic and pathophysiologic processes. Understanding the precise role(s) of specific Eicosanoid metabolites remains a significant challenge, but has led to the development of new pharmacologic strategies for treating NSAID-induced gastroenteropathy and IBD. Given the complex array of arachidonic acid metabolites, the development of more specific and potent inhibitors of these cyclooxygenase isoforms is important for future studies and possible therapeutic applications. Mice have been prepared that lack expression of COX-1 or COX-2. Once these animals have been carefully evaluated, understanding of the role of various pathways of Eicosanoid formation in gastrointestinal function, development, and epithelial growth regulation might be improved. Considerable progress has been made in the understanding of arachidonic acid metabolism and in Eicosanoid Receptor biology. The identification and characterization of an inducible cyclooxygenase isoform has led to important studies evaluating the role of this enzyme in inflammation, neoplasia, and NSAID-induced gastrointestinal injury. The demonstration that COX-2 overexpression in intestinal epithelial cells leads to specific phenotypic changes, such as increased adhesion and inhibition of apoptosis, indicates that this enzyme may alter the tumorigenic potential of epithelial cells and offers hope for the future development of improved chemopreventive agents.
Shigetada Nakanishi - One of the best experts on this subject based on the ideXlab platform.
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cloning and expression of cdna for a human thromboxane a2 Receptor
Nature, 1991Co-Authors: Masakazu Hirata, Yasunori Hayashi, Fumitaka Ushikubi, Yoshifumi Yokota, Ryoichiro Kageyama, Shigetada Nakanishi, Shuh NarumiyaAbstract:THROMBOXANE A2 is a very unstable arachidonate metabolite, yet a potent stimulator of platelet aggregation and a constrictor of vascular and respiratory smooth muscles1. It has been implicated as a mediator in diseases such as myocardial infarction, stroke and bronchial asthma2. Using a stable analogue of this compound we recently purified the human platelet thromboxane A2 Receptor to apparent homogeneity3. Using an oligonucleotide probe corresponding to its partial amino-acid sequence, we have obtained a complementary DNA clone encoding this Receptor from human placenta and a partial clone from cultured human megakaryocytic leukaemia cells. The placenta cDNA encodes a protein of 343 amino acids with seven putative transmembrane domains. The protein expressed in COS-7 cells binds drugs with affinities identical to those of the platelet Receptor, and that in Xenopus oocytes opens Ca2+-activated Cl- channel on agonist stimulation. Northern blot analysis and nucleotide sequences of the two clones suggest that an identical species of the thromboxane A2 Receptor is present in platelets and vascular tissues. This first report on the molecular structure of an Eicosanoid Receptor will promote the molecular pharmacology and pathophysiology of these bioactive compounds.
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Cloning and expression of cDNA for a human thromboxane A_2 Receptor
Nature, 1991Co-Authors: Masakazu Hirata, Yasunori Hayashi, Fumitaka Ushikubi, Yoshifumi Yokota, Ryoichiro Kageyama, Shigetada Nakanishi, Shuh NarumiyaAbstract:THROMBOXANE A_2 is a very unstable arachidonate metabolite, yet a potent stimulator of platelet aggregation and a constrictor of vascular and respiratory smooth muscles^1. It has been implicated as a mediator in diseases such as myocardial infarction, stroke and bronchial asthma^2. Using a stable analogue of this compound we recently purified the human platelet thromboxane A_2 Receptor to apparent homogeneity^3. Using an oligonucleotide probe corresponding to its partial amino-acid sequence, we have obtained a complementary DNA clone encoding this Receptor from human placenta and a partial clone from cultured human megakaryocytic leukaemia cells. The placenta cDNA encodes a protein of 343 amino acids with seven putative transmembrane domains. The protein expressed in COS-7 cells binds drugs with affinities identical to those of the platelet Receptor, and that in Xenopus oocytes opens Ca^2+-activated Cl^- channel on agonist stimulation. Northern blot analysis and nucleotide sequences of the two clones suggest that an identical species of the thromboxane A_2 Receptor is present in platelets and vascular tissues. This first report on the molecular structure of an Eicosanoid Receptor will promote the molecular pharmacology and pathophysiology of these bioactive compounds.
Yasunori Hayashi - One of the best experts on this subject based on the ideXlab platform.
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cloning and expression of cdna for a human thromboxane a2 Receptor
Nature, 1991Co-Authors: Masakazu Hirata, Yasunori Hayashi, Fumitaka Ushikubi, Yoshifumi Yokota, Ryoichiro Kageyama, Shigetada Nakanishi, Shuh NarumiyaAbstract:THROMBOXANE A2 is a very unstable arachidonate metabolite, yet a potent stimulator of platelet aggregation and a constrictor of vascular and respiratory smooth muscles1. It has been implicated as a mediator in diseases such as myocardial infarction, stroke and bronchial asthma2. Using a stable analogue of this compound we recently purified the human platelet thromboxane A2 Receptor to apparent homogeneity3. Using an oligonucleotide probe corresponding to its partial amino-acid sequence, we have obtained a complementary DNA clone encoding this Receptor from human placenta and a partial clone from cultured human megakaryocytic leukaemia cells. The placenta cDNA encodes a protein of 343 amino acids with seven putative transmembrane domains. The protein expressed in COS-7 cells binds drugs with affinities identical to those of the platelet Receptor, and that in Xenopus oocytes opens Ca2+-activated Cl- channel on agonist stimulation. Northern blot analysis and nucleotide sequences of the two clones suggest that an identical species of the thromboxane A2 Receptor is present in platelets and vascular tissues. This first report on the molecular structure of an Eicosanoid Receptor will promote the molecular pharmacology and pathophysiology of these bioactive compounds.
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Cloning and expression of cDNA for a human thromboxane A_2 Receptor
Nature, 1991Co-Authors: Masakazu Hirata, Yasunori Hayashi, Fumitaka Ushikubi, Yoshifumi Yokota, Ryoichiro Kageyama, Shigetada Nakanishi, Shuh NarumiyaAbstract:THROMBOXANE A_2 is a very unstable arachidonate metabolite, yet a potent stimulator of platelet aggregation and a constrictor of vascular and respiratory smooth muscles^1. It has been implicated as a mediator in diseases such as myocardial infarction, stroke and bronchial asthma^2. Using a stable analogue of this compound we recently purified the human platelet thromboxane A_2 Receptor to apparent homogeneity^3. Using an oligonucleotide probe corresponding to its partial amino-acid sequence, we have obtained a complementary DNA clone encoding this Receptor from human placenta and a partial clone from cultured human megakaryocytic leukaemia cells. The placenta cDNA encodes a protein of 343 amino acids with seven putative transmembrane domains. The protein expressed in COS-7 cells binds drugs with affinities identical to those of the platelet Receptor, and that in Xenopus oocytes opens Ca^2+-activated Cl^- channel on agonist stimulation. Northern blot analysis and nucleotide sequences of the two clones suggest that an identical species of the thromboxane A_2 Receptor is present in platelets and vascular tissues. This first report on the molecular structure of an Eicosanoid Receptor will promote the molecular pharmacology and pathophysiology of these bioactive compounds.