Identifying Clonidine-Displacing Substance

Atlas, Daphné

doi:10.1126/science.7939689

Cited by 24 publications

(11 citation statements)

References 13 publications

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“…Such an observation may be due to the separation of the imidazolinebinding protein from an associated protein or a small, endogenous organic ligand. The latter possibility is in line with the demonstration of endogenous substances such as clonidinedisplacing substance or agmatine which are postulated to be endogenous ligands for members of the family of imidazolinebinding proteins (3)(4)(5)(6)(7). This point also parallels several reports indicating the existence of endogenous substances that regulate MAO activity (34 -37).…”

Section: Discussionmentioning

confidence: 60%

“…Although many of these compounds interact with adrenergic receptors, they also produce ill-defined effects on ion transport, insulin secretion, and blood pressure regulation that are mediated by interactions with multiple, pharmacologically distinct imidazoline-binding proteins (1, 2, and references therein). 1 The imidazoline/guanidinium receptive sites also recognize endogenous substances that mimic some of these effects (3)(4)(5)(6)(7).…”

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confidence: 99%

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Imidazoline/Guanidinium Binding Domains on Monoamine Oxidases

Raddatz¹,

Parini²,

Lanier

1995

Journal of Biological Chemistry

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Pharmacologically active compounds with an imidazoline and/or guanidinium moiety are recognized with high affinity by a family of membrane-bound proteins collectively known as imidazoline binding sites or imidazoline/guanidinium receptive sites. Two such receptive sites may correspond to imidazoline binding domains identified on the A and B isoforms of monoamine oxidase (MAO), but the detection of monoamine oxidase isoforms in multiple tissues contrasts with the restricted expression of imidazoline-binding proteins.To address these issues, we determined the relationship between monoamine oxidase isoforms and subtypes of imidazoline-binding proteins in human tissues known to express one or both isoforms of MAO.

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Section: Discussionmentioning

confidence: 60%

mentioning

confidence: 99%

Imidazoline/Guanidinium Binding Domains on Monoamine Oxidases

Raddatz¹,

Parini²,

Lanier

1995

Journal of Biological Chemistry

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“…Typical RP‐HPLC traces obtained for bovine lung and brain with corresponding inhibition data ([ 3 H]clonidine from α 2 ‐adrenoceptors) are shown in Figures 1 and 2, respectively. The elution time demonstrated in Figures 1 and 2 (15–25 minutes) was selected firstly, because the main inhibition of [ 3 H]clonidine binding occurred in this region, and secondly, because the typical “3‐peak effect” observed by Atlas 4 was shown. Both tissues show the three main peaks eluting at times 17–18, 20, and 22–23 minutes, with the active displacing fraction eluting at 20–21 minutes (i.e., eluting with the middle peak of the three).…”

Section: Resultsmentioning

confidence: 99%

“…Agmatine (decarboxylated arginine) was proposed to be the endogenous ligand for imidazoline binding sites, 3 as it was isolated and purified from bovine brain and exhibited displacement of binding from α 2 ‐adrenoceptors and imidazoline binding sites. However, the molecular weight of agmatine (130 daltons) differs from that of CDS isolated by Atlas and Burnstein 4 (588 daltons), which suggests that there may be a family of clonidine‐displacing compounds.…”

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confidence: 82%

Comparison of Crude Methanolic CDS Extracts from Various Tissues

Parker

Hudson

Nutt

et al. 1999

Annals of the New York Academy of Sciences

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“…The chemical composition of CDS is still a matter of debate due to the discrepancies in extraction procedures and the sources of CDS extracts. However, what is currently known about the chemical entity of CDS is that it does not resemble that of a catecholamine nor a peptide [40]. Various groups have identified a number of contaminants present in CDS extracts that have survived the extraction process, including biogenic amines and complex β-carbolines [41,42].…”

Section: The Endogenous Extract At Imidazoline Binding Sites: Clonidimentioning

confidence: 99%

Borne Identity: Leading Endogenous Suspects at Imidazoline Binding Sites

Ghazaleh¹,

Tyacke²,

Hudson³

2015

J Neurol Neurosci

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The imidazoline binding sites (I-BS) represent a heterogenous family of receptors/sites that stemmed from studies investigating the hypotensive effect of the imidazoline compound clonidine [1]. Structure-affinity relationship studies complemented by functional analyses characterised three types of I-BS, denoted I 1 -BS, I 2 -BS (I 2A and I 2B ) and I 3 -BS [2]. Extensive research has established the involvement of central I 1 -BS in cardiovascular function [3]. Other reported functions include alleviating symptoms associated with metabolic syndrome X [4] and Huntington's Disease [5], promoting natriuresis [6], regulating intraocular pressure [7], and modulating mRNA expression for phenylethanolamine N-methyl transferase (PNMT) [8]. Furthermore, the expression of these sites was shown to be altered in conditions such as depression [9] and dysphoric premenstrual syndrome [10] AbstractOver the past few years, a vast amount of research has shed light on the pharmacology of imidazoline binding sites (I-BS). To date, at least three classes of imidazoline binding sites have been characterised in accordance to their localisation, drug selectivity, proposed signalling pathways and functional roles. The existence of these sites raises the question as to whether an endogenous modulator exists. The identification of an endogenous extract denoted as clonidine displacing substance prompted the search for the active ingredient capable of mimicking the action of selective ligands at these sites. A number of candidates have been isolated and their functional activities have been assessed at these sites. Such endogenous ligands include agmatine, imidazoleacetic acid ribotide and the β-carboline harmane. As of yet, no consensus has been made to confirm the identity of the endogenous ligand at I-BS. The current review collates and reports what is known about these substances and their functional significance at I-BS.

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Identifying Clonidine-Displacing Substance

Cited by 24 publications

References 13 publications

Imidazoline/Guanidinium Binding Domains on Monoamine Oxidases

Imidazoline/Guanidinium Binding Domains on Monoamine Oxidases

Comparison of Crude Methanolic CDS Extracts from Various Tissues

Borne Identity: Leading Endogenous Suspects at Imidazoline Binding Sites

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