The Experts below are selected from a list of 246 Experts worldwide ranked by ideXlab platform
Ikunobu Muramatsu - One of the best experts on this subject based on the ideXlab platform.
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Pharmacological evaluation of ocular β-adrenoceptors in rabbit by tissue segment Binding Method
Life Sciences, 2008Co-Authors: Takahiro Horinouchi, Shigeru Morishima, Yoshio Tanaka, Katsuo Koike, Soichi Miwa, Ikunobu MuramatsuAbstract:Abstract Aims This study evaluates ocular (iris, ciliary body and ciliary process) and nonocular (atria and lung) β-adrenoceptors in rabbit to characterize the plasma membrane β-adrenoceptors and Binding affinities of β-adrenoceptor antagonists. Main Methods The tissue segment Binding Method with a hydrophilic radioligand (−)-4-[3-t-butylamino-2-hydroxypropoxy]-[5,7-3H]benzimidazol-2-one ([3H]-CGP12177) was employed. Key findings Specific and saturable Binding of [3H]-CGP12177 to intact tissue segments was detected by using (±)-propranolol to define nonspecific Binding, showing a single population of plasma membrane Binding sites with high affinity. Competition experiments with selective β1- and β2-adrenoceptor antagonists revealed a single population of β2-adrenoceptors in ocular tissues and of β1-adrenoceptors in atria, but mixed populations of β1- and β2-adrenoceptors in 70% and 30%, respectively, in lung. A competition curve for timolol was biphasic in lung and its Binding affinity for β2-adrenoceptors was approximately 158-fold higher than for β1-adrenoceptors, indicating the β2-selectivity of timolol. In contrast, competition curves for stereoisomers of befunolol, carteolol, and propranolol were monophasic in all tissues. The (−)-enantiomers of these antagonists were more potent than corresponding (+)-enantiomers in displacing from [3H]-CGP12177 Binding, and the isomeric potency ratios of befunolol and carteolol were less than those of propranolol. Significance This study with tissue segment Binding Method suggests that the Binding affinity of (−)-enantiomers of β-adrenoceptor antagonists for plasma membrane β-adrenoceptors (β1-adrenoceptors of atria, β2-adrenoceptors of ocular tissues, and mixed β1-/β2-adrenoceptors of lung) is higher than that of corresponding (+)-enantiomers and their stereoselectivity is different between β-adrenoceptor antagonists.
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Pharmacological evaluation of ocular beta-adrenoceptors in rabbit by tissue segment Binding Method.
Life sciences, 2008Co-Authors: Takahiro Horinouchi, Shigeru Morishima, Yoshio Tanaka, Katsuo Koike, Soichi Miwa, Ikunobu MuramatsuAbstract:This study evaluates ocular (iris, ciliary body and ciliary process) and nonocular (atria and lung) beta-adrenoceptors in rabbit to characterize the plasma membrane beta-adrenoceptors and Binding affinities of beta-adrenoceptor antagonists. The tissue segment Binding Method with a hydrophilic radioligand (-)-4-[3-t-butylamino-2-hydroxypropoxy]-[5,7-(3)H]benzimidazol-2-one ([(3)H]-CGP12177) was employed. Specific and saturable Binding of [(3)H]-CGP12177 to intact tissue segments was detected by using (+/-)-propranolol to define nonspecific Binding, showing a single population of plasma membrane Binding sites with high affinity. Competition experiments with selective beta(1)- and beta(2)-adrenoceptor antagonists revealed a single population of beta(2)-adrenoceptors in ocular tissues and of beta(1)-adrenoceptors in atria, but mixed populations of beta(1)- and beta(2)-adrenoceptors in 70% and 30%, respectively, in lung. A competition curve for timolol was biphasic in lung and its Binding affinity for beta(2)-adrenoceptors was approximately 158-fold higher than for beta(1)-adrenoceptors, indicating the beta(2)-selectivity of timolol. In contrast, competition curves for stereoisomers of befunolol, carteolol, and propranolol were monophasic in all tissues. The (-)-enantiomers of these antagonists were more potent than corresponding (+)-enantiomers in displacing from [(3)H]-CGP12177 Binding, and the isomeric potency ratios of befunolol and carteolol were less than those of propranolol. This study with tissue segment Binding Method suggests that the Binding affinity of (-)-enantiomers of beta-adrenoceptor antagonists for plasma membrane beta-adrenoceptors (beta(1)-adrenoceptors of atria, beta(2)-adrenoceptors of ocular tissues, and mixed beta(1)-/beta(2)-adrenoceptors of lung) is higher than that of corresponding (+)-enantiomers and their stereoselectivity is different between beta-adrenoceptor antagonists.
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Pharmacological evaluation of plasma membrane β-adrenoceptors in rat hearts using the tissue segment Binding Method
Life sciences, 2006Co-Authors: Takahiro Horinouchi, Takashi Tanaka, Fumiko Suzuki, Shigeru Morishima, Yoshio Tanaka, Katsuo Koike, Ikunobu MuramatsuAbstract:Abstract This study evaluates β-adrenoceptors in rat atria and ventricle using the tissue segment Binding Method and compares the results with those obtained using conventional homogenate Binding assays. In studies with tissue segment Binding, the hydrophilic radioligand [ 3 H]-CGP12177 selectively bound to plasma membrane β-adrenoceptors, and the B max levels were significantly higher than those obtained with homogenate Binding. However, both Binding approaches revealed similar proportions of β 1 - and β 2 -adrenoceptors. The regional distribution of plasma membrane β 1 - and β 2 -adrenoceptors in rat hearts were also determined using tissue segment Binding. Abundance of β-adrenoceptors and proportion of β 1 -adrenoceptors were higher in atria than in ventricle, but there was no significant difference between right and left atria or within ventricle (right and left ventricle free walls, apex, and interventricular septum). To establish the ability of the tissue segment Binding Method to study β-adrenoceptor regulation such as the internalization of receptors, the effect of prolonged exposure of rat ventricle to (−)-isoprenaline was also investigated by using tissue segments and homogenate Binding. Incubation with (−)-isoprenaline for 1 h in vitro caused a concentration-dependent decrease in the density of β-adrenoceptors, predominantly β 2 -adrenoceptors, when assessed with tissue segment Binding Method. In contrast, the subtype-specific change after treatment with (−)-isoprenaline was not detected using homogenate Binding. In summary, the tissue segment Binding Method with [ 3 H]-CGP12177 enables a more precise quantitation of plasma membrane β 1 - and β 2 -adrenoceptors in rat hearts and is suitable for studying their regulation.
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Quantifying receptor properties: the tissue segment Binding Method - a powerful tool for the pharmacome analysis of native receptors.
Journal of Pharmacological Sciences, 2005Co-Authors: Ikunobu Muramatsu, Takashi Tanaka, Fumiko Suzuki, Yasuko Hiraizumi-hiraoka, Abu Syed Md Anisuzzaman, Hatsumi Yamamoto, Takahiro Horinouchi, Shigeru MorishimaAbstract:The radioligand Binding assay technique is an extremely powerful tool for studying receptors. It allows an analysis of the interactions of hormones, neurotransmitters, and related drugs with their receptors. Most of the Binding assays have widely been applied to crude membrane fractions prepared from many tissues, but in the conventional Method, there are some limitations such as a yield loss of receptor-bearing membranes and a change in receptor environment upon homogenization and fractionation. Recently, in order to overcome these problems, a Binding assay has been developed using intact tissue segments. This article presents a brief overview of the tissue segment Binding assay that has been developed mainly in our department. Practical guidelines for setting up this new assay are presented, including segment preparation, choice of appropriate radioligand, optimizing assay conditions, and appropriate Methods for data analysis. The unique advantages and disadvantages of the tissue segment Binding Method are discussed in comparison with those of conventional membrane Binding Methods. We suggest that the tissue segment Binding Method is a powerful tool for detecting the native properties of receptors occurring in tissues and cells without altering their environment.
Shigeru Morishima - One of the best experts on this subject based on the ideXlab platform.
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Pharmacological evaluation of ocular β-adrenoceptors in rabbit by tissue segment Binding Method
Life Sciences, 2008Co-Authors: Takahiro Horinouchi, Shigeru Morishima, Yoshio Tanaka, Katsuo Koike, Soichi Miwa, Ikunobu MuramatsuAbstract:Abstract Aims This study evaluates ocular (iris, ciliary body and ciliary process) and nonocular (atria and lung) β-adrenoceptors in rabbit to characterize the plasma membrane β-adrenoceptors and Binding affinities of β-adrenoceptor antagonists. Main Methods The tissue segment Binding Method with a hydrophilic radioligand (−)-4-[3-t-butylamino-2-hydroxypropoxy]-[5,7-3H]benzimidazol-2-one ([3H]-CGP12177) was employed. Key findings Specific and saturable Binding of [3H]-CGP12177 to intact tissue segments was detected by using (±)-propranolol to define nonspecific Binding, showing a single population of plasma membrane Binding sites with high affinity. Competition experiments with selective β1- and β2-adrenoceptor antagonists revealed a single population of β2-adrenoceptors in ocular tissues and of β1-adrenoceptors in atria, but mixed populations of β1- and β2-adrenoceptors in 70% and 30%, respectively, in lung. A competition curve for timolol was biphasic in lung and its Binding affinity for β2-adrenoceptors was approximately 158-fold higher than for β1-adrenoceptors, indicating the β2-selectivity of timolol. In contrast, competition curves for stereoisomers of befunolol, carteolol, and propranolol were monophasic in all tissues. The (−)-enantiomers of these antagonists were more potent than corresponding (+)-enantiomers in displacing from [3H]-CGP12177 Binding, and the isomeric potency ratios of befunolol and carteolol were less than those of propranolol. Significance This study with tissue segment Binding Method suggests that the Binding affinity of (−)-enantiomers of β-adrenoceptor antagonists for plasma membrane β-adrenoceptors (β1-adrenoceptors of atria, β2-adrenoceptors of ocular tissues, and mixed β1-/β2-adrenoceptors of lung) is higher than that of corresponding (+)-enantiomers and their stereoselectivity is different between β-adrenoceptor antagonists.
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Pharmacological evaluation of ocular beta-adrenoceptors in rabbit by tissue segment Binding Method.
Life sciences, 2008Co-Authors: Takahiro Horinouchi, Shigeru Morishima, Yoshio Tanaka, Katsuo Koike, Soichi Miwa, Ikunobu MuramatsuAbstract:This study evaluates ocular (iris, ciliary body and ciliary process) and nonocular (atria and lung) beta-adrenoceptors in rabbit to characterize the plasma membrane beta-adrenoceptors and Binding affinities of beta-adrenoceptor antagonists. The tissue segment Binding Method with a hydrophilic radioligand (-)-4-[3-t-butylamino-2-hydroxypropoxy]-[5,7-(3)H]benzimidazol-2-one ([(3)H]-CGP12177) was employed. Specific and saturable Binding of [(3)H]-CGP12177 to intact tissue segments was detected by using (+/-)-propranolol to define nonspecific Binding, showing a single population of plasma membrane Binding sites with high affinity. Competition experiments with selective beta(1)- and beta(2)-adrenoceptor antagonists revealed a single population of beta(2)-adrenoceptors in ocular tissues and of beta(1)-adrenoceptors in atria, but mixed populations of beta(1)- and beta(2)-adrenoceptors in 70% and 30%, respectively, in lung. A competition curve for timolol was biphasic in lung and its Binding affinity for beta(2)-adrenoceptors was approximately 158-fold higher than for beta(1)-adrenoceptors, indicating the beta(2)-selectivity of timolol. In contrast, competition curves for stereoisomers of befunolol, carteolol, and propranolol were monophasic in all tissues. The (-)-enantiomers of these antagonists were more potent than corresponding (+)-enantiomers in displacing from [(3)H]-CGP12177 Binding, and the isomeric potency ratios of befunolol and carteolol were less than those of propranolol. This study with tissue segment Binding Method suggests that the Binding affinity of (-)-enantiomers of beta-adrenoceptor antagonists for plasma membrane beta-adrenoceptors (beta(1)-adrenoceptors of atria, beta(2)-adrenoceptors of ocular tissues, and mixed beta(1)-/beta(2)-adrenoceptors of lung) is higher than that of corresponding (+)-enantiomers and their stereoselectivity is different between beta-adrenoceptor antagonists.
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Pharmacological evaluation of plasma membrane β-adrenoceptors in rat hearts using the tissue segment Binding Method
Life sciences, 2006Co-Authors: Takahiro Horinouchi, Takashi Tanaka, Fumiko Suzuki, Shigeru Morishima, Yoshio Tanaka, Katsuo Koike, Ikunobu MuramatsuAbstract:Abstract This study evaluates β-adrenoceptors in rat atria and ventricle using the tissue segment Binding Method and compares the results with those obtained using conventional homogenate Binding assays. In studies with tissue segment Binding, the hydrophilic radioligand [ 3 H]-CGP12177 selectively bound to plasma membrane β-adrenoceptors, and the B max levels were significantly higher than those obtained with homogenate Binding. However, both Binding approaches revealed similar proportions of β 1 - and β 2 -adrenoceptors. The regional distribution of plasma membrane β 1 - and β 2 -adrenoceptors in rat hearts were also determined using tissue segment Binding. Abundance of β-adrenoceptors and proportion of β 1 -adrenoceptors were higher in atria than in ventricle, but there was no significant difference between right and left atria or within ventricle (right and left ventricle free walls, apex, and interventricular septum). To establish the ability of the tissue segment Binding Method to study β-adrenoceptor regulation such as the internalization of receptors, the effect of prolonged exposure of rat ventricle to (−)-isoprenaline was also investigated by using tissue segments and homogenate Binding. Incubation with (−)-isoprenaline for 1 h in vitro caused a concentration-dependent decrease in the density of β-adrenoceptors, predominantly β 2 -adrenoceptors, when assessed with tissue segment Binding Method. In contrast, the subtype-specific change after treatment with (−)-isoprenaline was not detected using homogenate Binding. In summary, the tissue segment Binding Method with [ 3 H]-CGP12177 enables a more precise quantitation of plasma membrane β 1 - and β 2 -adrenoceptors in rat hearts and is suitable for studying their regulation.
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Quantifying receptor properties: the tissue segment Binding Method - a powerful tool for the pharmacome analysis of native receptors.
Journal of Pharmacological Sciences, 2005Co-Authors: Ikunobu Muramatsu, Takashi Tanaka, Fumiko Suzuki, Yasuko Hiraizumi-hiraoka, Abu Syed Md Anisuzzaman, Hatsumi Yamamoto, Takahiro Horinouchi, Shigeru MorishimaAbstract:The radioligand Binding assay technique is an extremely powerful tool for studying receptors. It allows an analysis of the interactions of hormones, neurotransmitters, and related drugs with their receptors. Most of the Binding assays have widely been applied to crude membrane fractions prepared from many tissues, but in the conventional Method, there are some limitations such as a yield loss of receptor-bearing membranes and a change in receptor environment upon homogenization and fractionation. Recently, in order to overcome these problems, a Binding assay has been developed using intact tissue segments. This article presents a brief overview of the tissue segment Binding assay that has been developed mainly in our department. Practical guidelines for setting up this new assay are presented, including segment preparation, choice of appropriate radioligand, optimizing assay conditions, and appropriate Methods for data analysis. The unique advantages and disadvantages of the tissue segment Binding Method are discussed in comparison with those of conventional membrane Binding Methods. We suggest that the tissue segment Binding Method is a powerful tool for detecting the native properties of receptors occurring in tissues and cells without altering their environment.
Takahiro Horinouchi - One of the best experts on this subject based on the ideXlab platform.
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Pharmacological evaluation of ocular β-adrenoceptors in rabbit by tissue segment Binding Method
Life Sciences, 2008Co-Authors: Takahiro Horinouchi, Shigeru Morishima, Yoshio Tanaka, Katsuo Koike, Soichi Miwa, Ikunobu MuramatsuAbstract:Abstract Aims This study evaluates ocular (iris, ciliary body and ciliary process) and nonocular (atria and lung) β-adrenoceptors in rabbit to characterize the plasma membrane β-adrenoceptors and Binding affinities of β-adrenoceptor antagonists. Main Methods The tissue segment Binding Method with a hydrophilic radioligand (−)-4-[3-t-butylamino-2-hydroxypropoxy]-[5,7-3H]benzimidazol-2-one ([3H]-CGP12177) was employed. Key findings Specific and saturable Binding of [3H]-CGP12177 to intact tissue segments was detected by using (±)-propranolol to define nonspecific Binding, showing a single population of plasma membrane Binding sites with high affinity. Competition experiments with selective β1- and β2-adrenoceptor antagonists revealed a single population of β2-adrenoceptors in ocular tissues and of β1-adrenoceptors in atria, but mixed populations of β1- and β2-adrenoceptors in 70% and 30%, respectively, in lung. A competition curve for timolol was biphasic in lung and its Binding affinity for β2-adrenoceptors was approximately 158-fold higher than for β1-adrenoceptors, indicating the β2-selectivity of timolol. In contrast, competition curves for stereoisomers of befunolol, carteolol, and propranolol were monophasic in all tissues. The (−)-enantiomers of these antagonists were more potent than corresponding (+)-enantiomers in displacing from [3H]-CGP12177 Binding, and the isomeric potency ratios of befunolol and carteolol were less than those of propranolol. Significance This study with tissue segment Binding Method suggests that the Binding affinity of (−)-enantiomers of β-adrenoceptor antagonists for plasma membrane β-adrenoceptors (β1-adrenoceptors of atria, β2-adrenoceptors of ocular tissues, and mixed β1-/β2-adrenoceptors of lung) is higher than that of corresponding (+)-enantiomers and their stereoselectivity is different between β-adrenoceptor antagonists.
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Pharmacological evaluation of ocular beta-adrenoceptors in rabbit by tissue segment Binding Method.
Life sciences, 2008Co-Authors: Takahiro Horinouchi, Shigeru Morishima, Yoshio Tanaka, Katsuo Koike, Soichi Miwa, Ikunobu MuramatsuAbstract:This study evaluates ocular (iris, ciliary body and ciliary process) and nonocular (atria and lung) beta-adrenoceptors in rabbit to characterize the plasma membrane beta-adrenoceptors and Binding affinities of beta-adrenoceptor antagonists. The tissue segment Binding Method with a hydrophilic radioligand (-)-4-[3-t-butylamino-2-hydroxypropoxy]-[5,7-(3)H]benzimidazol-2-one ([(3)H]-CGP12177) was employed. Specific and saturable Binding of [(3)H]-CGP12177 to intact tissue segments was detected by using (+/-)-propranolol to define nonspecific Binding, showing a single population of plasma membrane Binding sites with high affinity. Competition experiments with selective beta(1)- and beta(2)-adrenoceptor antagonists revealed a single population of beta(2)-adrenoceptors in ocular tissues and of beta(1)-adrenoceptors in atria, but mixed populations of beta(1)- and beta(2)-adrenoceptors in 70% and 30%, respectively, in lung. A competition curve for timolol was biphasic in lung and its Binding affinity for beta(2)-adrenoceptors was approximately 158-fold higher than for beta(1)-adrenoceptors, indicating the beta(2)-selectivity of timolol. In contrast, competition curves for stereoisomers of befunolol, carteolol, and propranolol were monophasic in all tissues. The (-)-enantiomers of these antagonists were more potent than corresponding (+)-enantiomers in displacing from [(3)H]-CGP12177 Binding, and the isomeric potency ratios of befunolol and carteolol were less than those of propranolol. This study with tissue segment Binding Method suggests that the Binding affinity of (-)-enantiomers of beta-adrenoceptor antagonists for plasma membrane beta-adrenoceptors (beta(1)-adrenoceptors of atria, beta(2)-adrenoceptors of ocular tissues, and mixed beta(1)-/beta(2)-adrenoceptors of lung) is higher than that of corresponding (+)-enantiomers and their stereoselectivity is different between beta-adrenoceptor antagonists.
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Pharmacological evaluation of plasma membrane β-adrenoceptors in rat hearts using the tissue segment Binding Method
Life sciences, 2006Co-Authors: Takahiro Horinouchi, Takashi Tanaka, Fumiko Suzuki, Shigeru Morishima, Yoshio Tanaka, Katsuo Koike, Ikunobu MuramatsuAbstract:Abstract This study evaluates β-adrenoceptors in rat atria and ventricle using the tissue segment Binding Method and compares the results with those obtained using conventional homogenate Binding assays. In studies with tissue segment Binding, the hydrophilic radioligand [ 3 H]-CGP12177 selectively bound to plasma membrane β-adrenoceptors, and the B max levels were significantly higher than those obtained with homogenate Binding. However, both Binding approaches revealed similar proportions of β 1 - and β 2 -adrenoceptors. The regional distribution of plasma membrane β 1 - and β 2 -adrenoceptors in rat hearts were also determined using tissue segment Binding. Abundance of β-adrenoceptors and proportion of β 1 -adrenoceptors were higher in atria than in ventricle, but there was no significant difference between right and left atria or within ventricle (right and left ventricle free walls, apex, and interventricular septum). To establish the ability of the tissue segment Binding Method to study β-adrenoceptor regulation such as the internalization of receptors, the effect of prolonged exposure of rat ventricle to (−)-isoprenaline was also investigated by using tissue segments and homogenate Binding. Incubation with (−)-isoprenaline for 1 h in vitro caused a concentration-dependent decrease in the density of β-adrenoceptors, predominantly β 2 -adrenoceptors, when assessed with tissue segment Binding Method. In contrast, the subtype-specific change after treatment with (−)-isoprenaline was not detected using homogenate Binding. In summary, the tissue segment Binding Method with [ 3 H]-CGP12177 enables a more precise quantitation of plasma membrane β 1 - and β 2 -adrenoceptors in rat hearts and is suitable for studying their regulation.
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Quantifying receptor properties: the tissue segment Binding Method - a powerful tool for the pharmacome analysis of native receptors.
Journal of Pharmacological Sciences, 2005Co-Authors: Ikunobu Muramatsu, Takashi Tanaka, Fumiko Suzuki, Yasuko Hiraizumi-hiraoka, Abu Syed Md Anisuzzaman, Hatsumi Yamamoto, Takahiro Horinouchi, Shigeru MorishimaAbstract:The radioligand Binding assay technique is an extremely powerful tool for studying receptors. It allows an analysis of the interactions of hormones, neurotransmitters, and related drugs with their receptors. Most of the Binding assays have widely been applied to crude membrane fractions prepared from many tissues, but in the conventional Method, there are some limitations such as a yield loss of receptor-bearing membranes and a change in receptor environment upon homogenization and fractionation. Recently, in order to overcome these problems, a Binding assay has been developed using intact tissue segments. This article presents a brief overview of the tissue segment Binding assay that has been developed mainly in our department. Practical guidelines for setting up this new assay are presented, including segment preparation, choice of appropriate radioligand, optimizing assay conditions, and appropriate Methods for data analysis. The unique advantages and disadvantages of the tissue segment Binding Method are discussed in comparison with those of conventional membrane Binding Methods. We suggest that the tissue segment Binding Method is a powerful tool for detecting the native properties of receptors occurring in tissues and cells without altering their environment.
Dimitrios A. Papaconstantopoulos - One of the best experts on this subject based on the ideXlab platform.
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Applications of the NRL tight-Binding Method to magnetic systems
Journal of Applied Physics, 2001Co-Authors: M. J. Mehl, Dimitrios A. Papaconstantopoulos, Igor Mazin, Naoum C. Bacalis, Warren E. PickettAbstract:The NRL developed tight-Binding Method has been very successful in describing the properties of nonmagnetic elemental metals and semiconductors with accuracy comparable to first-principles Methods. In this article we discuss extensions of the Method to magnetic systems. We first show that the Method correctly predicts equilibrium ground state structures, elastic constants, and phonon frequencies in ferromagnetic iron. We also show how the magnetic calculations can be extended to noncollinear systems, focusing on the electronic behavior of iron.
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The tight-Binding Method for interpolating first-principles total energy results
Journal of Phase Equilibria, 1997Co-Authors: Dimitrios A. Papaconstantopoulos, Michael J. MehlAbstract:This paper presents a new tight-Binding Method for the evaluation of the total energy in solids. The Method is calibrated to reproduce a limited set of first-principles results and is able to interpolate between different structures, at a cost which is orders of magnitude less than that required to do first-principles calculations on the same systems. The new Method has been tested on all transition metals and found to produce elastic constants, vacancy formation energies, surface energies, and phonon spectra in very good agreement with first-principles calculations and experiment. The extension of this scheme to transition metal aluminides is in progress and preliminary results using CoAl as a prototype system are presented.
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Application of a New Tight-Binding Method for Transition Metals: Manganese
Europhysics Letters (EPL), 1995Co-Authors: Michael J. Mehl, Dimitrios A. PapaconstantopoulosAbstract:A new tight-Binding total-energy Method, which has been shown to accurately predict ground-state properties of transition and noble metals, is applied to manganese, the element with the most complex ground-state structure among the d metals. We show that the tight-Binding Method correctly predicts the ground-state structure of Mn, and offers some insight into the magnetic properties of this state.
Yoshio Tanaka - One of the best experts on this subject based on the ideXlab platform.
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Pharmacological evaluation of ocular beta-adrenoceptors in rabbit by tissue segment Binding Method.
Life sciences, 2008Co-Authors: Takahiro Horinouchi, Shigeru Morishima, Yoshio Tanaka, Katsuo Koike, Soichi Miwa, Ikunobu MuramatsuAbstract:This study evaluates ocular (iris, ciliary body and ciliary process) and nonocular (atria and lung) beta-adrenoceptors in rabbit to characterize the plasma membrane beta-adrenoceptors and Binding affinities of beta-adrenoceptor antagonists. The tissue segment Binding Method with a hydrophilic radioligand (-)-4-[3-t-butylamino-2-hydroxypropoxy]-[5,7-(3)H]benzimidazol-2-one ([(3)H]-CGP12177) was employed. Specific and saturable Binding of [(3)H]-CGP12177 to intact tissue segments was detected by using (+/-)-propranolol to define nonspecific Binding, showing a single population of plasma membrane Binding sites with high affinity. Competition experiments with selective beta(1)- and beta(2)-adrenoceptor antagonists revealed a single population of beta(2)-adrenoceptors in ocular tissues and of beta(1)-adrenoceptors in atria, but mixed populations of beta(1)- and beta(2)-adrenoceptors in 70% and 30%, respectively, in lung. A competition curve for timolol was biphasic in lung and its Binding affinity for beta(2)-adrenoceptors was approximately 158-fold higher than for beta(1)-adrenoceptors, indicating the beta(2)-selectivity of timolol. In contrast, competition curves for stereoisomers of befunolol, carteolol, and propranolol were monophasic in all tissues. The (-)-enantiomers of these antagonists were more potent than corresponding (+)-enantiomers in displacing from [(3)H]-CGP12177 Binding, and the isomeric potency ratios of befunolol and carteolol were less than those of propranolol. This study with tissue segment Binding Method suggests that the Binding affinity of (-)-enantiomers of beta-adrenoceptor antagonists for plasma membrane beta-adrenoceptors (beta(1)-adrenoceptors of atria, beta(2)-adrenoceptors of ocular tissues, and mixed beta(1)-/beta(2)-adrenoceptors of lung) is higher than that of corresponding (+)-enantiomers and their stereoselectivity is different between beta-adrenoceptor antagonists.
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Pharmacological evaluation of ocular β-adrenoceptors in rabbit by tissue segment Binding Method
Life Sciences, 2008Co-Authors: Takahiro Horinouchi, Shigeru Morishima, Yoshio Tanaka, Katsuo Koike, Soichi Miwa, Ikunobu MuramatsuAbstract:Abstract Aims This study evaluates ocular (iris, ciliary body and ciliary process) and nonocular (atria and lung) β-adrenoceptors in rabbit to characterize the plasma membrane β-adrenoceptors and Binding affinities of β-adrenoceptor antagonists. Main Methods The tissue segment Binding Method with a hydrophilic radioligand (−)-4-[3-t-butylamino-2-hydroxypropoxy]-[5,7-3H]benzimidazol-2-one ([3H]-CGP12177) was employed. Key findings Specific and saturable Binding of [3H]-CGP12177 to intact tissue segments was detected by using (±)-propranolol to define nonspecific Binding, showing a single population of plasma membrane Binding sites with high affinity. Competition experiments with selective β1- and β2-adrenoceptor antagonists revealed a single population of β2-adrenoceptors in ocular tissues and of β1-adrenoceptors in atria, but mixed populations of β1- and β2-adrenoceptors in 70% and 30%, respectively, in lung. A competition curve for timolol was biphasic in lung and its Binding affinity for β2-adrenoceptors was approximately 158-fold higher than for β1-adrenoceptors, indicating the β2-selectivity of timolol. In contrast, competition curves for stereoisomers of befunolol, carteolol, and propranolol were monophasic in all tissues. The (−)-enantiomers of these antagonists were more potent than corresponding (+)-enantiomers in displacing from [3H]-CGP12177 Binding, and the isomeric potency ratios of befunolol and carteolol were less than those of propranolol. Significance This study with tissue segment Binding Method suggests that the Binding affinity of (−)-enantiomers of β-adrenoceptor antagonists for plasma membrane β-adrenoceptors (β1-adrenoceptors of atria, β2-adrenoceptors of ocular tissues, and mixed β1-/β2-adrenoceptors of lung) is higher than that of corresponding (+)-enantiomers and their stereoselectivity is different between β-adrenoceptor antagonists.
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Pharmacological evaluation of plasma membrane β-adrenoceptors in rat hearts using the tissue segment Binding Method
Life sciences, 2006Co-Authors: Takahiro Horinouchi, Takashi Tanaka, Fumiko Suzuki, Shigeru Morishima, Yoshio Tanaka, Katsuo Koike, Ikunobu MuramatsuAbstract:Abstract This study evaluates β-adrenoceptors in rat atria and ventricle using the tissue segment Binding Method and compares the results with those obtained using conventional homogenate Binding assays. In studies with tissue segment Binding, the hydrophilic radioligand [ 3 H]-CGP12177 selectively bound to plasma membrane β-adrenoceptors, and the B max levels were significantly higher than those obtained with homogenate Binding. However, both Binding approaches revealed similar proportions of β 1 - and β 2 -adrenoceptors. The regional distribution of plasma membrane β 1 - and β 2 -adrenoceptors in rat hearts were also determined using tissue segment Binding. Abundance of β-adrenoceptors and proportion of β 1 -adrenoceptors were higher in atria than in ventricle, but there was no significant difference between right and left atria or within ventricle (right and left ventricle free walls, apex, and interventricular septum). To establish the ability of the tissue segment Binding Method to study β-adrenoceptor regulation such as the internalization of receptors, the effect of prolonged exposure of rat ventricle to (−)-isoprenaline was also investigated by using tissue segments and homogenate Binding. Incubation with (−)-isoprenaline for 1 h in vitro caused a concentration-dependent decrease in the density of β-adrenoceptors, predominantly β 2 -adrenoceptors, when assessed with tissue segment Binding Method. In contrast, the subtype-specific change after treatment with (−)-isoprenaline was not detected using homogenate Binding. In summary, the tissue segment Binding Method with [ 3 H]-CGP12177 enables a more precise quantitation of plasma membrane β 1 - and β 2 -adrenoceptors in rat hearts and is suitable for studying their regulation.