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Your search keyword '"Kurose, Hitoshi"' showing total 29 results
Start Over Author "Kurose, Hitoshi" Publisher japanese pharmacological society
29 results on '"Kurose, Hitoshi"'

27. Beta-blockers show inverse agonism to a novel constitutively active mutant of beta1-adrenoceptor.

Author

Ahmed M, Muntasir HA, Hossain M, Ishiguro M, Komiyama T, Muramatsu I, Kurose H, and Nagatomo T

Subjects
Cell Line, Cyclic AMP metabolism, Humans, Ligands, Protein Binding, Adrenergic beta-1 Receptor Agonists, Adrenergic beta-Antagonists pharmacology, Point Mutation, Receptors, Adrenergic, beta-1 genetics
Abstract

We obtained a new mutant of the beta(1)-adrenergic receptor (beta(1)-AR) by point mutations that can constitutively activate beta(1)-AR. Aspartate104 of the beta(1)-AR in the 2nd transmembrane was replaced with alanine. The beta(1)-AR mutant expressed in human embryonic kidney (HEK)-293 cells displayed high level of constitutive activity with respect to wild-type (P<0.05), which could be partially inhibited by some beta-blockers. The constitutive activity of the mutant was confirmed by the finding that the enhanced activity is dependent on the level of receptor expression. The results of this study might have interesting implications for future studies aiming at elucidating the activation process of the beta(1)-AR as well as the mechanism of action of beta-blockers.

Published
2006
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28. Heterotrimeric G protein G alpha13-induced induction of cytokine mRNAs through two distinct pathways in cardiac fibroblasts.

Author

Nagamatsu Y, Nishida M, Onohara N, Fukutomi M, Maruyama Y, Kobayashi H, Sato Y, and Kurose H

Subjects
Animals, Calcium metabolism, Egtazic Acid analogs & derivatives, Egtazic Acid pharmacology, Fibroblasts cytology, Fibroblasts drug effects, Heart Ventricles cytology, Interleukin-1 metabolism, Interleukin-6 metabolism, NF-kappa B metabolism, Onium Compounds pharmacology, RNA, Messenger metabolism, Rats, Rats, Sprague-Dawley, Reactive Oxygen Species metabolism, Cytokines metabolism, Fibroblasts metabolism, GTP-Binding Protein alpha Subunits, G12-G13 metabolism
Abstract

Overexpression of constitutively active (CA)-G alpha13 significantly increased the expression of interleukin (IL)-1beta and IL-6 mRNAs and proteins in rat cardiac fibroblasts. IL-1beta mRNA induction by CA-G alpha13 was suppressed by diphenyleneiodonium (DPI), an NADPH oxidase inhibitor, but not by BAPTA-AM, an intracellular Ca2+ chelator. In contrast, IL-6 mRNA induction by CA-G alpha13 was suppressed by BAPTA-AM but not by DPI. However, both IL-1beta and IL-6 mRNA induction was suppressed by nuclear factor kappaB (NF-kappaB) inhibitors. The CA-G alpha13-induced NF-kappaB activation was suppressed by DPI and BAPTA-AM, but not C3 toxin and the Rho-kinase inhibitor Y27632. IL-6 mRNA induction by CA-G alpha13 was suppressed by SK&F96365 (1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride), an inhibitor of receptor-activated nonselective cation channels, and the expression of CA-G alpha13 increased basal Ca2+ influx. These results suggest that G alpha13 regulates IL-1beta mRNA induction through the reactive oxygen species-NF-kappaB pathway, while it regulates IL-6 mRNA induction through the Ca2+-NF-kappaB pathway.

Published
2006
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29. Enhanced cAMP response of naturally occurring mutant of human beta3-adrenergic receptor.

Author

Isogaya M, Nagao T, and Kurose H

Subjects
Adenylate Cyclase Toxin, Adenylyl Cyclases metabolism, Adrenergic beta-Agonists pharmacology, Animals, COS Cells, Dose-Response Relationship, Drug, HeLa Cells, Humans, Isoenzymes metabolism, Pertussis Toxin, Propanolamines pharmacology, Radioligand Assay, Receptors, Adrenergic, beta-3 biosynthesis, Receptors, Adrenergic, beta-3 metabolism, Transfection, Virulence Factors, Bordetella pharmacology, Cyclic AMP physiology, Receptors, Adrenergic, beta-3 genetics
Abstract

We have examined the functional significance of the naturally occurring mutation at position 64 of human beta3-adrenergic receptor (beta3AR), which changes the amino acid from tryptophan to arginine (W64R-beta3AR). The affinities of betaAR agonists for W64R-beta3AR expressed in COS-7 cells were not significantly different from those for wild type beta3AR. When two receptors are expressed at various expression levels, and stimulated with CGP12177A, they showed essentially the same EC50 values and maximal responses. Overexpression of Gi and Go, or the treatment with pertussis toxin did not affect the agonist-induced cAMP response, suggesting that Gi and Go did not contribute to the beta3AR-induced cAMP response. However, the enhanced cAMP response was observed when W64R-beta3AR was coexpressed with the adenylyl cyclase type III isoform, and stimulated by CGP12177A and isoproterenol. These results indicate that the cAMP response of W64R-beta3AR can be enhanced under the particular condition that adenylyl cyclase type III was coexpressed.

Published
2002
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