Activation of P2Y receptor enhances high-molecular compound absorption from rat ileum
While there are no reports concerning the effects of extracellular nucleotides on the intestinal absorption of drugs, it is well known that extracellular nucleotides are important regulators of intestinal epithelial ion transport. This report using fluorescein isothiocyanate dextran 4000 (FD‐4) as t...
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Veröffentlicht in: | Journal of pharmacy and pharmacology 2006-02, Vol.58 (2), p.195-200 |
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description | While there are no reports concerning the effects of extracellular nucleotides on the intestinal absorption of drugs, it is well known that extracellular nucleotides are important regulators of intestinal epithelial ion transport. This report using fluorescein isothiocyanate dextran 4000 (FD‐4) as the model compound is the first to investigate the effects of purine nucleotides on absorption of poorly absorbed drugs from intestine. ATP enhanced the absorption of FD‐4 from rat ileum in a concentration‐dependent manner. ADP also enhanced the absorption of FD‐4. Other purine nucleotides (adenosine, AMP, UTP and UDP) did not show an absorption‐enhancing effect. The absorption‐enhancing effect by ATP was inhibited by suramin and pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulfonate (PPADS), which are known P2 receptor antagonists. Additionally, 2‐methylthio ATP (a P2Y receptor agonist) enhanced the absorption of FD‐4, but α,β‐methylene ATP (a P2X receptor agonist) did not. These findings suggest that activation of the P2Y receptor may improve the absorption of water‐soluble and high‐molecular compounds from the ileum. |
doi_str_mv | 10.1211/jpp.58.2.0006 |
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This report using fluorescein isothiocyanate dextran 4000 (FD‐4) as the model compound is the first to investigate the effects of purine nucleotides on absorption of poorly absorbed drugs from intestine. ATP enhanced the absorption of FD‐4 from rat ileum in a concentration‐dependent manner. ADP also enhanced the absorption of FD‐4. Other purine nucleotides (adenosine, AMP, UTP and UDP) did not show an absorption‐enhancing effect. The absorption‐enhancing effect by ATP was inhibited by suramin and pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulfonate (PPADS), which are known P2 receptor antagonists. Additionally, 2‐methylthio ATP (a P2Y receptor agonist) enhanced the absorption of FD‐4, but α,β‐methylene ATP (a P2X receptor agonist) did not. These findings suggest that activation of the P2Y receptor may improve the absorption of water‐soluble and high‐molecular compounds from the ileum.</description><identifier>ISSN: 0022-3573</identifier><identifier>EISSN: 2042-7158</identifier><identifier>DOI: 10.1211/jpp.58.2.0006</identifier><identifier>PMID: 16451747</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adenosine Triphosphate - analogs & derivatives ; Adenosine Triphosphate - pharmacology ; Animals ; Dextrans - blood ; Dextrans - pharmacokinetics ; Fluorescein-5-isothiocyanate - analogs & derivatives ; Fluorescein-5-isothiocyanate - pharmacokinetics ; Ileum - drug effects ; Ileum - metabolism ; Intestinal Absorption - drug effects ; Male ; Nucleotides - pharmacology ; Purinergic P2 Receptor Agonists ; Purinergic P2 Receptor Antagonists ; Pyridoxal Phosphate - analogs & derivatives ; Pyridoxal Phosphate - pharmacology ; Rats ; Rats, Wistar ; Receptors, Purinergic P2 - metabolism ; Suramin - pharmacology ; Thionucleotides - pharmacology</subject><ispartof>Journal of pharmacy and pharmacology, 2006-02, Vol.58 (2), p.195-200</ispartof><rights>2006 Royal Pharmaceutical Society of Great Britain</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4777-674ec1c91e01692df5201a38727deb9162bdb7cf452eaab298306db5943e96e93</citedby><cites>FETCH-LOGICAL-c4777-674ec1c91e01692df5201a38727deb9162bdb7cf452eaab298306db5943e96e93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1211%2Fjpp.58.2.0006$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1211%2Fjpp.58.2.0006$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16451747$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kinoshita, Natsumi</creatorcontrib><creatorcontrib>Takahashi, Tomoko</creatorcontrib><creatorcontrib>Tada, Shoko</creatorcontrib><creatorcontrib>Shinozuka, Kazumasa</creatorcontrib><creatorcontrib>Mizuno, Nobuyasu</creatorcontrib><creatorcontrib>Takahashi, Koichi</creatorcontrib><title>Activation of P2Y receptor enhances high-molecular compound absorption from rat ileum</title><title>Journal of pharmacy and pharmacology</title><addtitle>J Pharm Pharmacol</addtitle><description>While there are no reports concerning the effects of extracellular nucleotides on the intestinal absorption of drugs, it is well known that extracellular nucleotides are important regulators of intestinal epithelial ion transport. This report using fluorescein isothiocyanate dextran 4000 (FD‐4) as the model compound is the first to investigate the effects of purine nucleotides on absorption of poorly absorbed drugs from intestine. ATP enhanced the absorption of FD‐4 from rat ileum in a concentration‐dependent manner. ADP also enhanced the absorption of FD‐4. Other purine nucleotides (adenosine, AMP, UTP and UDP) did not show an absorption‐enhancing effect. The absorption‐enhancing effect by ATP was inhibited by suramin and pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulfonate (PPADS), which are known P2 receptor antagonists. Additionally, 2‐methylthio ATP (a P2Y receptor agonist) enhanced the absorption of FD‐4, but α,β‐methylene ATP (a P2X receptor agonist) did not. These findings suggest that activation of the P2Y receptor may improve the absorption of water‐soluble and high‐molecular compounds from the ileum.</description><subject>Adenosine Triphosphate - analogs & derivatives</subject><subject>Adenosine Triphosphate - pharmacology</subject><subject>Animals</subject><subject>Dextrans - blood</subject><subject>Dextrans - pharmacokinetics</subject><subject>Fluorescein-5-isothiocyanate - analogs & derivatives</subject><subject>Fluorescein-5-isothiocyanate - pharmacokinetics</subject><subject>Ileum - drug effects</subject><subject>Ileum - metabolism</subject><subject>Intestinal Absorption - drug effects</subject><subject>Male</subject><subject>Nucleotides - pharmacology</subject><subject>Purinergic P2 Receptor Agonists</subject><subject>Purinergic P2 Receptor Antagonists</subject><subject>Pyridoxal Phosphate - analogs & derivatives</subject><subject>Pyridoxal Phosphate - pharmacology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors, Purinergic P2 - metabolism</subject><subject>Suramin - pharmacology</subject><subject>Thionucleotides - pharmacology</subject><issn>0022-3573</issn><issn>2042-7158</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtv1DAUhS0EokPLki3yil0G-_qVLKsRbYFRGakPYGU5zg2TksSpnQD99007I7rr6m6-c3TuR8g7zpYcOP94MwxLlS9hyRjTL8gCmITMcJW_JAvGADKhjDggb1K6mQmjtX5NDriWihtpFuTq2I_NHzc2oaehphv4SSN6HMYQKfZb13tMdNv82mZdaNFPrYvUh24IU19RV6YQh8dsHUNHoxtp0-LUHZFXtWsTvt3fQ3J18ulydZatv51-Xh2vMy-NMZk2Ej33BUfGdQFVrYBxJ3IDpsKy4BrKqjS-lgrQuRKKXDBdlaqQAguNhTgkH3a9Qwy3E6bRdk3y2LauxzAlq40GCSBmMNuBPoaUItZ2iE3n4p3lzD54tLNHq3IL9sHjzL_fF09lh9UTvRc3A7AD_s4P3z3fZr9szja5Mk8rmjTiv_8hF3_PS4VR9vv5qV39uD75WlxIuxb3TAiNpg</recordid><startdate>200602</startdate><enddate>200602</enddate><creator>Kinoshita, Natsumi</creator><creator>Takahashi, Tomoko</creator><creator>Tada, Shoko</creator><creator>Shinozuka, Kazumasa</creator><creator>Mizuno, Nobuyasu</creator><creator>Takahashi, Koichi</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200602</creationdate><title>Activation of P2Y receptor enhances high-molecular compound absorption from rat ileum</title><author>Kinoshita, Natsumi ; Takahashi, Tomoko ; Tada, Shoko ; Shinozuka, Kazumasa ; Mizuno, Nobuyasu ; Takahashi, Koichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4777-674ec1c91e01692df5201a38727deb9162bdb7cf452eaab298306db5943e96e93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adenosine Triphosphate - analogs & derivatives</topic><topic>Adenosine Triphosphate - pharmacology</topic><topic>Animals</topic><topic>Dextrans - blood</topic><topic>Dextrans - pharmacokinetics</topic><topic>Fluorescein-5-isothiocyanate - analogs & derivatives</topic><topic>Fluorescein-5-isothiocyanate - pharmacokinetics</topic><topic>Ileum - drug effects</topic><topic>Ileum - metabolism</topic><topic>Intestinal Absorption - drug effects</topic><topic>Male</topic><topic>Nucleotides - pharmacology</topic><topic>Purinergic P2 Receptor Agonists</topic><topic>Purinergic P2 Receptor Antagonists</topic><topic>Pyridoxal Phosphate - analogs & derivatives</topic><topic>Pyridoxal Phosphate - pharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptors, Purinergic P2 - metabolism</topic><topic>Suramin - pharmacology</topic><topic>Thionucleotides - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kinoshita, Natsumi</creatorcontrib><creatorcontrib>Takahashi, Tomoko</creatorcontrib><creatorcontrib>Tada, Shoko</creatorcontrib><creatorcontrib>Shinozuka, Kazumasa</creatorcontrib><creatorcontrib>Mizuno, Nobuyasu</creatorcontrib><creatorcontrib>Takahashi, Koichi</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of pharmacy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kinoshita, Natsumi</au><au>Takahashi, Tomoko</au><au>Tada, Shoko</au><au>Shinozuka, Kazumasa</au><au>Mizuno, Nobuyasu</au><au>Takahashi, Koichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation of P2Y receptor enhances high-molecular compound absorption from rat ileum</atitle><jtitle>Journal of pharmacy and pharmacology</jtitle><addtitle>J Pharm Pharmacol</addtitle><date>2006-02</date><risdate>2006</risdate><volume>58</volume><issue>2</issue><spage>195</spage><epage>200</epage><pages>195-200</pages><issn>0022-3573</issn><eissn>2042-7158</eissn><abstract>While there are no reports concerning the effects of extracellular nucleotides on the intestinal absorption of drugs, it is well known that extracellular nucleotides are important regulators of intestinal epithelial ion transport. This report using fluorescein isothiocyanate dextran 4000 (FD‐4) as the model compound is the first to investigate the effects of purine nucleotides on absorption of poorly absorbed drugs from intestine. ATP enhanced the absorption of FD‐4 from rat ileum in a concentration‐dependent manner. ADP also enhanced the absorption of FD‐4. Other purine nucleotides (adenosine, AMP, UTP and UDP) did not show an absorption‐enhancing effect. The absorption‐enhancing effect by ATP was inhibited by suramin and pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulfonate (PPADS), which are known P2 receptor antagonists. Additionally, 2‐methylthio ATP (a P2Y receptor agonist) enhanced the absorption of FD‐4, but α,β‐methylene ATP (a P2X receptor agonist) did not. These findings suggest that activation of the P2Y receptor may improve the absorption of water‐soluble and high‐molecular compounds from the ileum.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>16451747</pmid><doi>10.1211/jpp.58.2.0006</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Oxford University Press Journals All Titles (1996-Current) |
subjects | Adenosine Triphosphate - analogs & derivatives Adenosine Triphosphate - pharmacology Animals Dextrans - blood Dextrans - pharmacokinetics Fluorescein-5-isothiocyanate - analogs & derivatives Fluorescein-5-isothiocyanate - pharmacokinetics Ileum - drug effects Ileum - metabolism Intestinal Absorption - drug effects Male Nucleotides - pharmacology Purinergic P2 Receptor Agonists Purinergic P2 Receptor Antagonists Pyridoxal Phosphate - analogs & derivatives Pyridoxal Phosphate - pharmacology Rats Rats, Wistar Receptors, Purinergic P2 - metabolism Suramin - pharmacology Thionucleotides - pharmacology |
title | Activation of P2Y receptor enhances high-molecular compound absorption from rat ileum |
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