|Imidazoleacetic acid-ribotide: an endogenous ligand that stimulates imidazol(in)e receptors.|
|PMID: 15365189 Owner: NLM Status: MEDLINE|
|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.|
|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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|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|
|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|
|Created Date: 2004-09-15 Completed Date: 2004-10-26 Revised Date: 2014-09-18|
Medline Journal Info:
|Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States|
|Languages: eng Pagination: 13677-82 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
Antibodies / immunology
Arachidonic Acid / metabolism
Brain Stem / cytology
Calcium / metabolism
Enzyme-Linked Immunosorbent Assay
Hypertension / chemically induced
Imidazoles / chemistry, immunology, pharmacology*
Insulin / secretion
Islets of Langerhans / secretion
Neurons / metabolism
Receptors, Drug / agonists*, metabolism
Ribosemonophosphates / chemistry, immunology, pharmacology*
|HL 44514/HL/NHLBI NIH HHS; NS 28012/NS/NINDS NIH HHS; R01 HL044514/HL/NHLBI NIH HHS|
|0/Antibodies; 0/Imidazoles; 0/Imidazoline Receptors; 0/Insulin; 0/Ligands; 0/Receptors, Drug; 0/Ribosemonophosphates; 0/imidazoleacetic acid ribotide; 27YG812J1I/Arachidonic Acid; SY7Q814VUP/Calcium|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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