Imidazoleacetic Acid-Ribotide: An Endogenous Ligand That Stimulates Imidazol(in)e Receptors
We identified the previously unknown structures of ribosylated imidazoleacetic acids in rat, bovine, and human tissues to be imidazole-4-acetic acid-ribotide (IAA-RP) and its metabolite, imidazole-4-acetic acid-riboside. We also found that IAA-RP has physicochemical properties similar to those of an...
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creator | Prell, George D. Martinelli, Giorgio P. Holstein, Gay R. Matulić-Adamić, Jasenka Watanabe, Kyoichi A. Susan L. F. Chan Morgan, Noel G. Haxhiu, Musa A. Ernsberger, Paul Black, James W. |
description | We identified the previously unknown structures of ribosylated imidazoleacetic acids in rat, bovine, and human tissues to be imidazole-4-acetic acid-ribotide (IAA-RP) and its metabolite, imidazole-4-acetic acid-riboside. We also found that IAA-RP has physicochemical properties similar to those of an unidentified substance(s) extracted from mammalian tissues that interacts with imidazol(in)e receptors (I-Rs). ["Imidazoline," by consensus (International Union of Pharmacology), includes imidazole, imidazoline, and related compounds. We demonstrate that the imidazole IAA-RP acts at I-Rs, and because few (if any) imidazolines exist in vivo, we have adopted the term "imidazol(in)e-Rs."] The latter regulate multiple functions in the CNS and periphery. We now show that IAA-RP (i) is present in brain and tissue extracts that exhibit I-R activity; (ii) is present in neurons of brainstem areas, including the rostroventrolateral medulla, a region where drugs active at I-Rs are known to modulate blood pressure; (iii) is present within synaptosome-enriched fractions of brain where its release is Ca2+-dependent, consistent with transmitter function; (iv) produces I-R-linked effects in vitro (e.g., arachidonic acid and insulin release) that are blocked by relevant antagonists; and (v) produces hypertension when microinjected into the rostroventrolateral medulla. Our data also suggest that IAA-RP may interact with a novel imidazol(in)e-like receptor at this site. We propose that IAA-RP is a neuroregulator acting via I-Rs. |
doi_str_mv | 10.1073/pnas.0404846101 |
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F. Chan ; Morgan, Noel G. ; Haxhiu, Musa A. ; Ernsberger, Paul ; Black, James W.</creator><creatorcontrib>Prell, George D. ; Martinelli, Giorgio P. ; Holstein, Gay R. ; Matulić-Adamić, Jasenka ; Watanabe, Kyoichi A. ; Susan L. F. Chan ; Morgan, Noel G. ; Haxhiu, Musa A. ; Ernsberger, Paul ; Black, James W.</creatorcontrib><description>We identified the previously unknown structures of ribosylated imidazoleacetic acids in rat, bovine, and human tissues to be imidazole-4-acetic acid-ribotide (IAA-RP) and its metabolite, imidazole-4-acetic acid-riboside. We also found that IAA-RP has physicochemical properties similar to those of an unidentified substance(s) extracted from mammalian tissues that interacts with imidazol(in)e receptors (I-Rs). ["Imidazoline," by consensus (International Union of Pharmacology), includes imidazole, imidazoline, and related compounds. We demonstrate that the imidazole IAA-RP acts at I-Rs, and because few (if any) imidazolines exist in vivo, we have adopted the term "imidazol(in)e-Rs."] The latter regulate multiple functions in the CNS and periphery. We now show that IAA-RP (i) is present in brain and tissue extracts that exhibit I-R activity; (ii) is present in neurons of brainstem areas, including the rostroventrolateral medulla, a region where drugs active at I-Rs are known to modulate blood pressure; (iii) is present within synaptosome-enriched fractions of brain where its release is Ca2+-dependent, consistent with transmitter function; (iv) produces I-R-linked effects in vitro (e.g., arachidonic acid and insulin release) that are blocked by relevant antagonists; and (v) produces hypertension when microinjected into the rostroventrolateral medulla. Our data also suggest that IAA-RP may interact with a novel imidazol(in)e-like receptor at this site. We propose that IAA-RP is a neuroregulator acting via I-Rs.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0404846101</identifier><identifier>PMID: 15365189</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Adrenal Medulla - metabolism ; Agonists ; Animals ; Antibodies - immunology ; Antibody Specificity ; Arachidonic Acid - metabolism ; Biological Sciences ; Brain Stem - cytology ; Calcium - metabolism ; Central nervous system ; Enzyme-Linked Immunosorbent Assay ; Humans ; Hypertension - chemically induced ; Imidazoles - chemistry ; Imidazoles - immunology ; Imidazoles - pharmacology ; Imidazoline Receptors ; Insulin ; Insulin - metabolism ; Insulin antibodies ; Insulin Secretion ; Islets of Langerhans - metabolism ; Isomerism ; Isomers ; Ligands ; Molecular Structure ; Neurons ; Neurons - metabolism ; PC12 Cells ; Rats ; Receptors ; Receptors, Drug - agonists ; Receptors, Drug - metabolism ; Ribosemonophosphates - chemistry ; Ribosemonophosphates - immunology ; Ribosemonophosphates - pharmacology ; Vehicles</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2004-09, Vol.101 (37), p.13677-13682</ispartof><rights>Copyright 1993/2004 The National Academy of Sciences of the United States of America</rights><rights>Copyright © 2004, The National Academy of Sciences 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c437t-463381d7d1ae2e951e4e12351a0553e3c383b81d22e6a62702e29870531d758e3</citedby><cites>FETCH-LOGICAL-c437t-463381d7d1ae2e951e4e12351a0553e3c383b81d22e6a62702e29870531d758e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/101/37.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3373370$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3373370$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15365189$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Prell, George D.</creatorcontrib><creatorcontrib>Martinelli, Giorgio P.</creatorcontrib><creatorcontrib>Holstein, Gay R.</creatorcontrib><creatorcontrib>Matulić-Adamić, Jasenka</creatorcontrib><creatorcontrib>Watanabe, Kyoichi A.</creatorcontrib><creatorcontrib>Susan L. F. Chan</creatorcontrib><creatorcontrib>Morgan, Noel G.</creatorcontrib><creatorcontrib>Haxhiu, Musa A.</creatorcontrib><creatorcontrib>Ernsberger, Paul</creatorcontrib><creatorcontrib>Black, James W.</creatorcontrib><title>Imidazoleacetic Acid-Ribotide: An Endogenous Ligand That Stimulates Imidazol(in)e Receptors</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>We identified the previously unknown structures of ribosylated imidazoleacetic acids in rat, bovine, and human tissues to be imidazole-4-acetic acid-ribotide (IAA-RP) and its metabolite, imidazole-4-acetic acid-riboside. We also found that IAA-RP has physicochemical properties similar to those of an unidentified substance(s) extracted from mammalian tissues that interacts with imidazol(in)e receptors (I-Rs). ["Imidazoline," by consensus (International Union of Pharmacology), includes imidazole, imidazoline, and related compounds. We demonstrate that the imidazole IAA-RP acts at I-Rs, and because few (if any) imidazolines exist in vivo, we have adopted the term "imidazol(in)e-Rs."] The latter regulate multiple functions in the CNS and periphery. We now show that IAA-RP (i) is present in brain and tissue extracts that exhibit I-R activity; (ii) is present in neurons of brainstem areas, including the rostroventrolateral medulla, a region where drugs active at I-Rs are known to modulate blood pressure; (iii) is present within synaptosome-enriched fractions of brain where its release is Ca2+-dependent, consistent with transmitter function; (iv) produces I-R-linked effects in vitro (e.g., arachidonic acid and insulin release) that are blocked by relevant antagonists; and (v) produces hypertension when microinjected into the rostroventrolateral medulla. Our data also suggest that IAA-RP may interact with a novel imidazol(in)e-like receptor at this site. We propose that IAA-RP is a neuroregulator acting via I-Rs.</description><subject>Adrenal Medulla - metabolism</subject><subject>Agonists</subject><subject>Animals</subject><subject>Antibodies - immunology</subject><subject>Antibody Specificity</subject><subject>Arachidonic Acid - metabolism</subject><subject>Biological Sciences</subject><subject>Brain Stem - cytology</subject><subject>Calcium - metabolism</subject><subject>Central nervous system</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Humans</subject><subject>Hypertension - chemically induced</subject><subject>Imidazoles - chemistry</subject><subject>Imidazoles - immunology</subject><subject>Imidazoles - pharmacology</subject><subject>Imidazoline Receptors</subject><subject>Insulin</subject><subject>Insulin - metabolism</subject><subject>Insulin antibodies</subject><subject>Insulin Secretion</subject><subject>Islets of Langerhans - metabolism</subject><subject>Isomerism</subject><subject>Isomers</subject><subject>Ligands</subject><subject>Molecular Structure</subject><subject>Neurons</subject><subject>Neurons - metabolism</subject><subject>PC12 Cells</subject><subject>Rats</subject><subject>Receptors</subject><subject>Receptors, Drug - agonists</subject><subject>Receptors, Drug - metabolism</subject><subject>Ribosemonophosphates - chemistry</subject><subject>Ribosemonophosphates - immunology</subject><subject>Ribosemonophosphates - pharmacology</subject><subject>Vehicles</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEFrGzEQRkVoSRy3515K0TE5bDLSSCttIQcTkjZgKKTpqQch744dhfWuWckhya-PjN24PRUG5jDv-wYeY58EnAkweL7qfDwDBcqqUoA4YCMBlShKVcE7NgKQprBKqiN2HOMDAFTawiE7EhpLLWw1Yr9vlqHxL31LvqYUaj6pQ1PchlmfQkNf-aTjV13TL6jr15FPw8J3Db-794n_TGG5bn2iyP90nITulPgt1bRK_RA_sPdz30b6uNtj9uv66u7yezH98e3mcjItaoUmFapEtKIxjfAkqdKCFAmJWnjQGglrtDjLgJRU-lIakCQra0BjDmlLOGYX297VerakpqYuDb51qyEs_fDseh_cv5cu3LtF_-iyAps_jdn5Nl8PfYwDzd-iAtxGs9todnvNOfHl7497fuc1A3wHbJL7OuHQOIGlMRk5_Q_i5uu2TfSUMvt5yz7ELPYNRjR5AF8BN6ObWg</recordid><startdate>20040914</startdate><enddate>20040914</enddate><creator>Prell, George D.</creator><creator>Martinelli, Giorgio P.</creator><creator>Holstein, Gay R.</creator><creator>Matulić-Adamić, Jasenka</creator><creator>Watanabe, Kyoichi A.</creator><creator>Susan L. F. Chan</creator><creator>Morgan, Noel G.</creator><creator>Haxhiu, Musa A.</creator><creator>Ernsberger, Paul</creator><creator>Black, James W.</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><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>5PM</scope></search><sort><creationdate>20040914</creationdate><title>Imidazoleacetic Acid-Ribotide: An Endogenous Ligand That Stimulates Imidazol(in)e Receptors</title><author>Prell, George D. ; Martinelli, Giorgio P. ; Holstein, Gay R. ; Matulić-Adamić, Jasenka ; Watanabe, Kyoichi A. ; Susan L. F. 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F. Chan</creatorcontrib><creatorcontrib>Morgan, Noel G.</creatorcontrib><creatorcontrib>Haxhiu, Musa A.</creatorcontrib><creatorcontrib>Ernsberger, Paul</creatorcontrib><creatorcontrib>Black, James W.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Prell, George D.</au><au>Martinelli, Giorgio P.</au><au>Holstein, Gay R.</au><au>Matulić-Adamić, Jasenka</au><au>Watanabe, Kyoichi A.</au><au>Susan L. F. Chan</au><au>Morgan, Noel G.</au><au>Haxhiu, Musa A.</au><au>Ernsberger, Paul</au><au>Black, James W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Imidazoleacetic Acid-Ribotide: An Endogenous Ligand That Stimulates Imidazol(in)e Receptors</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2004-09-14</date><risdate>2004</risdate><volume>101</volume><issue>37</issue><spage>13677</spage><epage>13682</epage><pages>13677-13682</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>We identified the previously unknown structures of ribosylated imidazoleacetic acids in rat, bovine, and human tissues to be imidazole-4-acetic acid-ribotide (IAA-RP) and its metabolite, imidazole-4-acetic acid-riboside. We also found that IAA-RP has physicochemical properties similar to those of an unidentified substance(s) extracted from mammalian tissues that interacts with imidazol(in)e receptors (I-Rs). ["Imidazoline," by consensus (International Union of Pharmacology), includes imidazole, imidazoline, and related compounds. We demonstrate that the imidazole IAA-RP acts at I-Rs, and because few (if any) imidazolines exist in vivo, we have adopted the term "imidazol(in)e-Rs."] The latter regulate multiple functions in the CNS and periphery. We now show that IAA-RP (i) is present in brain and tissue extracts that exhibit I-R activity; (ii) is present in neurons of brainstem areas, including the rostroventrolateral medulla, a region where drugs active at I-Rs are known to modulate blood pressure; (iii) is present within synaptosome-enriched fractions of brain where its release is Ca2+-dependent, consistent with transmitter function; (iv) produces I-R-linked effects in vitro (e.g., arachidonic acid and insulin release) that are blocked by relevant antagonists; and (v) produces hypertension when microinjected into the rostroventrolateral medulla. Our data also suggest that IAA-RP may interact with a novel imidazol(in)e-like receptor at this site. We propose that IAA-RP is a neuroregulator acting via I-Rs.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>15365189</pmid><doi>10.1073/pnas.0404846101</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adrenal Medulla - metabolism Agonists Animals Antibodies - immunology Antibody Specificity Arachidonic Acid - metabolism Biological Sciences Brain Stem - cytology Calcium - metabolism Central nervous system Enzyme-Linked Immunosorbent Assay Humans Hypertension - chemically induced Imidazoles - chemistry Imidazoles - immunology Imidazoles - pharmacology Imidazoline Receptors Insulin Insulin - metabolism Insulin antibodies Insulin Secretion Islets of Langerhans - metabolism Isomerism Isomers Ligands Molecular Structure Neurons Neurons - metabolism PC12 Cells Rats Receptors Receptors, Drug - agonists Receptors, Drug - metabolism Ribosemonophosphates - chemistry Ribosemonophosphates - immunology Ribosemonophosphates - pharmacology Vehicles |
title | Imidazoleacetic Acid-Ribotide: An Endogenous Ligand That Stimulates Imidazol(in)e Receptors |
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