Document Detail


Imidazoleacetic acid-ribotide: an endogenous ligand that stimulates imidazol(in)e receptors.
MedLine Citation:
PMID:  15365189     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
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:
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:
Created Date:  2004-09-15     Completed Date:  2004-10-26     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13677-82     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA. george.prell@mssm.edu
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MeSH Terms
Descriptor/Qualifier:
Adrenal Medulla / 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:
HL 44514/HL/NHLBI NIH HHS; NS 28012/NS/NINDS NIH HHS; R01 HL044514-08/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
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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