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Immunohistochemistry for Anti-diabetes Drug, Alogliptin Using a Newly Prepared Monoclonal Antibody: Its Precise Localization in Rat Small Intestine

Knowledge of time sequence of localization of drugs in cells and tissues of animals may help in developing a better understanding of the actual overall pharmacokinetics of the drugs. We produced monoclonal antibody (mAb) against alogliptin (AG), a dipeptidyl peptidase-4 (DPP-4) inhibitor, conjugated...

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Autores principales: Yamamoto, Yuta, Yamamoto, Yutaro, Saita, Tetsuya, Shin, Masashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434317/
https://www.ncbi.nlm.nih.gov/pubmed/30923413
http://dx.doi.org/10.1267/ahc.18036
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author Yamamoto, Yuta
Yamamoto, Yutaro
Saita, Tetsuya
Shin, Masashi
author_facet Yamamoto, Yuta
Yamamoto, Yutaro
Saita, Tetsuya
Shin, Masashi
author_sort Yamamoto, Yuta
collection PubMed
description Knowledge of time sequence of localization of drugs in cells and tissues of animals may help in developing a better understanding of the actual overall pharmacokinetics of the drugs. We produced monoclonal antibody (mAb) against alogliptin (AG), a dipeptidyl peptidase-4 (DPP-4) inhibitor, conjugated to BSA with N-(γ-maleimidobutyryloxy)-succinimide. The mAb was specific for AG and did not cross-react with sitagliptin, vancomycin or amoxicillin. The mAb enabled us to develop an immunohistochemical method for detecting the localization of AG in the rat small intestine. One hour after a single oral administration of AG, immunohistochemistry revealed that the immunoreactivity of AG was observed in almost all of cells and tissues of the duodenum. The microvilli of the absorptive epithelial cells were moderately stained. The staining pattern of AG at jejunum and ilium was almost the same as that of duodenum, but the staining intensity, especially at absorptive epithelial cells and intestinal gland epithelial cells, became stronger towards the distal part of the small intestine. These results suggested that AG may be more actively absorbed from the lower part of the small intestine than in the upper part. It may affect the function of cells with membrane-bound DPP-4 because it was reported that membrane-bound form of DPP-4 exists in the microvilli of the absorptive epithelial cells.
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spelling pubmed-64343172019-03-28 Immunohistochemistry for Anti-diabetes Drug, Alogliptin Using a Newly Prepared Monoclonal Antibody: Its Precise Localization in Rat Small Intestine Yamamoto, Yuta Yamamoto, Yutaro Saita, Tetsuya Shin, Masashi Acta Histochem Cytochem Regular Article Knowledge of time sequence of localization of drugs in cells and tissues of animals may help in developing a better understanding of the actual overall pharmacokinetics of the drugs. We produced monoclonal antibody (mAb) against alogliptin (AG), a dipeptidyl peptidase-4 (DPP-4) inhibitor, conjugated to BSA with N-(γ-maleimidobutyryloxy)-succinimide. The mAb was specific for AG and did not cross-react with sitagliptin, vancomycin or amoxicillin. The mAb enabled us to develop an immunohistochemical method for detecting the localization of AG in the rat small intestine. One hour after a single oral administration of AG, immunohistochemistry revealed that the immunoreactivity of AG was observed in almost all of cells and tissues of the duodenum. The microvilli of the absorptive epithelial cells were moderately stained. The staining pattern of AG at jejunum and ilium was almost the same as that of duodenum, but the staining intensity, especially at absorptive epithelial cells and intestinal gland epithelial cells, became stronger towards the distal part of the small intestine. These results suggested that AG may be more actively absorbed from the lower part of the small intestine than in the upper part. It may affect the function of cells with membrane-bound DPP-4 because it was reported that membrane-bound form of DPP-4 exists in the microvilli of the absorptive epithelial cells. JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY 2019-02-28 2019-02-23 /pmc/articles/PMC6434317/ /pubmed/30923413 http://dx.doi.org/10.1267/ahc.18036 Text en 2019 The Japan Society of Histochemistry and Cytochemistry This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Regular Article
Yamamoto, Yuta
Yamamoto, Yutaro
Saita, Tetsuya
Shin, Masashi
Immunohistochemistry for Anti-diabetes Drug, Alogliptin Using a Newly Prepared Monoclonal Antibody: Its Precise Localization in Rat Small Intestine
title Immunohistochemistry for Anti-diabetes Drug, Alogliptin Using a Newly Prepared Monoclonal Antibody: Its Precise Localization in Rat Small Intestine
title_full Immunohistochemistry for Anti-diabetes Drug, Alogliptin Using a Newly Prepared Monoclonal Antibody: Its Precise Localization in Rat Small Intestine
title_fullStr Immunohistochemistry for Anti-diabetes Drug, Alogliptin Using a Newly Prepared Monoclonal Antibody: Its Precise Localization in Rat Small Intestine
title_full_unstemmed Immunohistochemistry for Anti-diabetes Drug, Alogliptin Using a Newly Prepared Monoclonal Antibody: Its Precise Localization in Rat Small Intestine
title_short Immunohistochemistry for Anti-diabetes Drug, Alogliptin Using a Newly Prepared Monoclonal Antibody: Its Precise Localization in Rat Small Intestine
title_sort immunohistochemistry for anti-diabetes drug, alogliptin using a newly prepared monoclonal antibody: its precise localization in rat small intestine
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434317/
https://www.ncbi.nlm.nih.gov/pubmed/30923413
http://dx.doi.org/10.1267/ahc.18036
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