Imidazoleacetic acid-ribotide: An endogenous ligand that stimulates imidazol(in)e receptors
AUTOR(ES)
Prell, George D.
FONTE
National Academy of Sciences
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=518812Documentos Relacionados
- Nitrolinoleic acid: An endogenous peroxisome proliferator-activated receptor γ ligand
- Identification of an endogenous ligand that activates pregnane X receptor-mediated sterol clearance
- Imidazoline receptors in the heart: a novel target and a novel mechanism of action that involves atrial natriuretic peptides
- Ligand Induction of Retinoic Acid Receptors Alters an Acute Infection by Murine Cytomegalovirus†
- Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids.