Imidazoleacetic Acid

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George D. Prell - One of the best experts on this subject based on the ideXlab platform.

  • Imidazoleacetic Acid ribotide induces depression of synaptic responses in hippocampus through activation of imidazoline receptors
    Journal of Neurophysiology, 2011
    Co-Authors: Ozlem Bozdagi, Giorgio P. Martinelli, George D. Prell, X B Wang, V L Friedrich, George W Huntley, G R Holstein
    Abstract:

    Imidazole-4-acetic Acid-ribotide (IAA-RP), an endogenous agonist at imidazoline receptors (I-Rs), is a putative neurotransmitter/regulator in mammalian brain. We studied the effects of IAA-RP on ex...

  • Vestibular neurons in the rat contain Imidazoleacetic Acid-ribotide, a putative neurotransmitter involved in blood pressure regulation.
    The Journal of comparative neurology, 2007
    Co-Authors: Giovanni Martinelli, Victor L Friedrich, George D. Prell
    Abstract:

    A substantial body of research has led to the recognition that the vestibular system participates in blood pressure modulation during active movements and changes in posture, and that this modulation is effected at least partly by the caudal vestibular nuclei. The I-4 isomer of Imidazoleacetic Acid-ribotide (IAA-RP) is a putative neurotransmitter/modulator that is thought to be an endogenous regulator of general sympathetic drive, particularly systemic blood pressure. The present study employed immunofluorescence and light and electron microscopic immunocytochemistry to visualize IAA-RP in the vestibular nuclei of adult male rats. The results demonstrate IAA-RP immunolabeling of subpopulations of vestibular neurons in the descending nucleus and the caudal half of the medial nucleus, with scattered immunostained vestibular neurons also present more rostrally. On the basis of double immunofluorescence staining for IAA-RP and calbindin, many of these ribotide-immunoreactive neurons appear to be innervated by cerebellar Purkinje cell afferents. Ultrastructural observations in the caudal vestibular nuclei confirm the IAA-RP immunolocalization in cell bodies and dendritic processes, and in some myelinated axons and presynaptic boutons. The regional distribution of IAA-RP immunoreactivity corresponds to the location of vestibular neurons involved in autonomic functions. The presence of IAA-RP in those neurons suggests that they participate specifically in vestibulo-autonomic regulation of blood pressure. The localization of immunostain in processes and terminals suggests that vestibulo-autonomic activity is subject to local feedback control. Overall, the observations offer a chemoanatomic basis for understanding the vestibular side effects commonly experienced by patients treated with clonidine and other imidazoline-related drugs.

  • distribution and cellular localization of Imidazoleacetic Acid ribotide an endogenous ligand at imidazol in e and adrenergic receptors in rat brain
    Journal of Chemical Neuroanatomy, 2007
    Co-Authors: Victor L Friedrich, Giorgio P. Martinelli, George D. Prell
    Abstract:

    Imidazoleacetic Acid-ribotide (IAA-RP) is a putative neurotransmitter/modulator recently discovered in mammalian brain. The present study examines the distribution of IAA-RP in the rat CNS using a highly specific antiserum raised in rabbit against IAA-RP with immunostaining of aldehyde-fixed rat CNS. IAA-RP-immunoreactive neurons were present throughout the neuraxis; neuroglia were not labeled. In each region, only a subset of the neuronal pool was immunostained. In the forebrain, ribotide-immunolabeled neurons were common in neocortex, in hippocampal formation, and in subcortical structures including basal ganglia, thalamus and hypothalamus. Labeling was prominent in limbic areas including olfactory bulb, basal forebrain, pyriform cortex and amygdala. In the mid- and hindbrain, immunolabeled neurons were concentrated in specific nuclei and, in some areas, in specific subregions of those nuclei. Structures of the motor system, including cranial nerve motor nuclei, precerebellar nuclei, the substantia nigra, and the red nucleus were clearly labeled. Staining was intense in cells and/or puncta in the rostral and caudal ventrolateral medullary reticular formation, nucleus tractus solitarius and the caudal vestibular nuclear complex. Within neurons, the ribotide was found predominantly in somata and dendrites; some myelinated axons and occasional synaptic terminals were also immunostained. These data indicate that IAA-RP contributes to the neurochemical phenotype of many neuronal populations and further supports our suggestion that, in autonomic structures, IAA-RP may serve as a chemical mediator in complex circuits involved in blood pressure regulation and, more generally, sympathetic drive.

  • Imidazoleacetic Acid ribotide an endogenous ligand that stimulates imidazol in e receptors
    Proceedings of the National Academy of Sciences of the United States of America, 2004
    Co-Authors: George D. Prell, Giorgio P. Martinelli, Jasenka Matulicadamic, Kyoichi A Watanabe, Sue L F Chan, Noel G Morgan, Musa A Haxhiu, Paul Ernsberger
    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.

  • Imidazoleacetic Acid a γ aminobutyric Acid receptor agonist can be formed in rat brain by oxidation of histamine
    Journal of Neurochemistry, 2002
    Co-Authors: Boban Thomas, George D. Prell
    Abstract:

    It is generally accepted that in mammalian brain histamine is metabolized solely by histamine methyltransferase (HMT), to form tele-methylhistamine, then oxidized to tele-methylImidazoleacetic Acid. However, histamine's oxidative metabolite in the periphery, Imidazoleacetic Acid (IAA), is also present in brain and CSF, and its levels in brain increase after inhibition of HMT. To reinvestigate if brain has the capacity to oxidize histamine and form IAA, conscious rats were injected with [ 3 H]histamine (10 ng ), either into the lateral ventricles or cisterna magna, and decapitated 30 min later. In brains of saline-treated rats, most radioactivity recovered was due to telemethylhistamine and tele-methylImidazoleacetic Acid. However, significant amounts of tritiated IAA and its metabolites, IAA-ribotide and IAA-riboside, were consistently recovered. In rats pretreated with metoprine, an inhibitor of HMT, labeled IAA and its metabolites usually comprised the majority of histamine's tritiated metabolites. [ 3 H]Histamine given intracisternally produced only trace amounts of oxidative metabolites. Formation of IAA, a potent GABA-A agonist with numerous neurochemical and behavioral effects, from minute quantities of histamine in brain indicates a need for reevaluation of histamine's metabolic pathway or pathways in brain and suggests a novel mechanism for interactions between histamine and the GABAergic system.

Barbara Pawlak - One of the best experts on this subject based on the ideXlab platform.

Piotr Drozdzewski - One of the best experts on this subject based on the ideXlab platform.

Anders Nordstrom - One of the best experts on this subject based on the ideXlab platform.

  • a quantitative lc ms method targeting urinary 1 methyl 4 Imidazoleacetic Acid for safety monitoring of the global histamine turnover in clinical studies
    Analytical and Bioanalytical Chemistry, 2014
    Co-Authors: Johan Kolmert, Benita Forngren, Johan Lindberg, J Ohd, K M Aberg, Gunnar Nilsson, Thomas Moritz, Anders Nordstrom
    Abstract:

    Anaphylaxis is a potentially life-threatening condition triggered mainly by the release of inflammatory mediators, notably histamine. In pharmaceutical research, drug discovery, and clinical evaluation, it may be necessary to accurately assess the potential of a compound, event, or disorder to promote the release of histamine. In contrast to the measurement of plasma histamine, determination of the stable metabolite 1-methyl-4-Imidazoleacetic Acid (tele-MIAA) in urine provides a noninvasive and more reliable methodology to monitor histamine release. This study presents a repeatable high-performance liquid chromatography coupled to electrospray mass spectrometry (LC–ESI–MS) method where tele-MIAA is baseline separated from its structural isomer 1-methyl-5-Imidazoleacetic Acid (pi-MIAA) and an unknown in human urine. The ion-pairing chromatography method, in reversed-phase mode, based on 0.5 mM tridecafluoroheptanoic Acid demonstrated high repeatability and was applied in a clinical development program that comprised a large number of clinical samples from different cohorts. The inter- and intra-run precision of the method for tele-MIAA were 8.4 and 4.3 %, respectively, at the mean urinary concentration level, while method accuracy was between −16.2 and 8.0 % across the linear concentration range of 22–1,111 ng mL−1. Overall, method precision was greater than that reported in previously published methods and enabled the identification of gender differences that were independent of age or demography. The median concentration measured in female subjects was 3.0 μmol mmol−1 of creatinine, and for male subjects, it was 2.1 μmol mmol−1 of creatinine. The results demonstrate that the method provides unprecedented accuracy, precision, and practicality for the measurement of tele-MIAA in large clinical settings.

J Ohd - One of the best experts on this subject based on the ideXlab platform.

  • a quantitative lc ms method targeting urinary 1 methyl 4 Imidazoleacetic Acid for safety monitoring of the global histamine turnover in clinical studies
    Analytical and Bioanalytical Chemistry, 2014
    Co-Authors: Johan Kolmert, Benita Forngren, Johan Lindberg, J Ohd, K M Aberg, Gunnar Nilsson, Thomas Moritz, Anders Nordstrom
    Abstract:

    Anaphylaxis is a potentially life-threatening condition triggered mainly by the release of inflammatory mediators, notably histamine. In pharmaceutical research, drug discovery, and clinical evaluation, it may be necessary to accurately assess the potential of a compound, event, or disorder to promote the release of histamine. In contrast to the measurement of plasma histamine, determination of the stable metabolite 1-methyl-4-Imidazoleacetic Acid (tele-MIAA) in urine provides a noninvasive and more reliable methodology to monitor histamine release. This study presents a repeatable high-performance liquid chromatography coupled to electrospray mass spectrometry (LC–ESI–MS) method where tele-MIAA is baseline separated from its structural isomer 1-methyl-5-Imidazoleacetic Acid (pi-MIAA) and an unknown in human urine. The ion-pairing chromatography method, in reversed-phase mode, based on 0.5 mM tridecafluoroheptanoic Acid demonstrated high repeatability and was applied in a clinical development program that comprised a large number of clinical samples from different cohorts. The inter- and intra-run precision of the method for tele-MIAA were 8.4 and 4.3 %, respectively, at the mean urinary concentration level, while method accuracy was between −16.2 and 8.0 % across the linear concentration range of 22–1,111 ng mL−1. Overall, method precision was greater than that reported in previously published methods and enabled the identification of gender differences that were independent of age or demography. The median concentration measured in female subjects was 3.0 μmol mmol−1 of creatinine, and for male subjects, it was 2.1 μmol mmol−1 of creatinine. The results demonstrate that the method provides unprecedented accuracy, precision, and practicality for the measurement of tele-MIAA in large clinical settings.