| Imidazoleacetic acid-ribotide: an endogenous ligand that stimulates imidazol(in)e receptors. | |
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MedLine Citation:
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PMID: 15365189 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 Ca(2+)-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. |
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Authors:
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George D Prell; Giorgio P Martinelli; Gay R Holstein; Jasenka Matulić-Adamić; Kyoichi A Watanabe; Susan L F Chan; Noel G Morgan; Musa A Haxhiu; Paul Ernsberger |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. Date: 2004-09-13 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 101 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2004 Sep |
Date Detail:
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Created Date: 2004-09-15 Completed Date: 2004-10-26 Revised Date: 2013-04-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 13677-82 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA. george.prell@mssm.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenal Medulla
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metabolism Animals Antibodies / immunology Antibody Specificity Arachidonic Acid / metabolism Brain Stem / cytology Calcium / metabolism Enzyme-Linked Immunosorbent Assay Humans Hypertension / chemically induced Imidazoles / chemistry, immunology, pharmacology* Imidazoline Receptors Insulin / secretion Islets of Langerhans / secretion Isomerism Ligands Molecular Structure Neurons / metabolism PC12 Cells Rats Receptors, Drug / agonists*, metabolism Ribosemonophosphates / chemistry, immunology, pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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HL 44514/HL/NHLBI NIH HHS; NS 28012/NS/NINDS NIH HHS; R01 HL044514-08/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies; 0/Imidazoles; 0/Imidazoline Receptors; 0/Insulin; 0/Ligands; 0/Receptors, Drug; 0/Ribosemonophosphates; 0/imidazoleacetic acid ribotide; 506-32-1/Arachidonic Acid; 7440-70-2/Calcium |
| Comments/Corrections | |
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