Pharmacological modulation of immunoreactive imidazoline receptor proteins in rat brain: relationship with non‐adrenoceptor [<sup>3</sup>H]‐idazoxan binding sites

Escribá, Pablo V.; Alemany, Regina; Sastre, Magdalena; Olmos, Gabriel; Ozaita, Andrés; Garcı́a-Sevilla, Jesús A.

doi:10.1111/j.1476-5381.1996.tb15640.x

Cited by 35 publications

(56 citation statements)

References 38 publications

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“…The actual protocol used for "crude" membrane preparation was selected because it was similar to that used by other authors to show the existence of I 2 -binding sites located on proteins distinct from MAO (Escriba et al, 1994(Escriba et al, , 1995(Escriba et al, , 1996.…”

Section: Resultsmentioning

confidence: 99%

Analysis of the Pharmacological and Molecular Heterogeneity of I₂-Imidazoline-Binding Proteins using Monoamine Oxidase-Deficient Mouse Models

et al. 2000

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The I 2 subgroup of imidazoline-binding sites was identified as monoamine oxidases (MAOs), but it is unclear whether there are I 2 -binding sites located on proteins distinct from MAOs. photolabeled three proteins with apparent molecular masses of ϳ28 (liver), ϳ61 (brain), and ϳ55 kDa (liver and brain). The photolabeling of each protein was blocked by the imidazoline cirazoline (10 M). Photolabeling of the ϳ61-and ϳ55-kDa proteins was not observed in MAO A and B KO mice, respectively. In contrast, photolabeling of the liver ϳ28-kDa protein was still observed in MAO-deficient mice, indicating that this protein is unrelated to MAOs. These data indicate that I 2 imidazoline-binding sites identified by [ 3 H]idazoxan reside solely on MAO B. The binding sites on MAO A and the liver ϳ28-kDa protein may represent additional subtypes of the family of the imidazoline-binding sites.

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Section: Resultsmentioning

confidence: 99%

Analysis of the Pharmacological and Molecular Heterogeneity of I₂-Imidazoline-Binding Proteins using Monoamine Oxidase-Deficient Mouse Models

et al. 2000

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“…On the other hand, recent evidences suggest that the pharmacological subtype called I2B-imidazoline receptor in the rat brain corresponds to more than one molecular entity and that the related immunoreactive imidazoline receptor proteins (~ 29/30, ~ 45 and ~ 66 kDa) contribute differentially to the modulation of non-adrenoceptor [3H]-idazoxan binding sites after drug treatment (Escribfi et al 1996). In this context, it could be proposed that the I2A-imidazoline receptor subtype labelled by [3H]-idazoxan in the rabbit brain is also heterogeneous in nature and related to similar and/or different immunoreactive proteins (~ 30, 57 and ~ 66 kDa) (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…4). The apparent molecular masses of these peptides were ~ 29/30 (double band), ~45 and ~66 kDa, as described previously (Escribfi et al 1994(Escribfi et al , 1996. In rabbit cortical membranes the anti-imidazoline receptor antibody detected proteins of ~ 30, ~ 57 and ~ 66 kDa (Fig.…”

Section: Different Pharmacological Properties Of I2-imidazoline Recepmentioning

confidence: 98%

Pharmacological and molecular discrimination of brain I2-imidazoline receptor subtypes

Olmos

Alemany

Garcı́a-Sevilla

1996

Naunyn-Schmiedeberg's Arch Pharmacol

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I2-imidazoline receptors labelled with [3H]-idazoxan in the rabbit and rat brains displayed high and low affinity, respectively, for the guanidide amiloride; reinforcing the previous definition of I2A-imidazoline receptors expressed in the rabbit brain and I2B-imidazoline receptors expressed in the rat brain. Other drugs tested displayed biphasic curves in competition experiments, indicating the existence of high and low affinity sites for both subtypes of I2-imidazoline receptors. Among the drugs studied, bromoxidine, moxonidine, (+)- and (-)-medetomidine and clorgyline were more potent on the high and/or low affinity sites of I2B-than on their corresponding of I2A-imidazoline receptors (KiH ratios 20 to 65). No correlation was found for the potencies of the drugs tested at the low affinity sites of both I2-imidazoline receptor subtypes. Preincubation (30 min at 25 degrees C) with 10(-6) M clorgyline reduced by 60% the Bmax of [3H]-idazoxan binding to I2B-imidazoline receptors in the rat brain, but it did not affect the binding parameters of the radioligand saturation curves to I2A-imidazoline receptors in the rabbit brain. These results indicated that I2A- and I2B-imidazoline receptor subtypes differ in the pharmacological profiles of their high and low affinity sites and in the ability to irreversibly bind clorgyline. In rat cortical membranes western blot detection of immunoreactive imidazoline receptors proteins revealed a double band of approximately 29/30 kDa and two less intense bands of approximately 45 and approximately 66 kDa. In rabbit cortical membranes the antibody used detected proteins of approximately 30, approximately 57 and approximately 66 kDa. It is suggested that different imidazoline receptor proteins (approximately 45 vs approximately 57 kDa) may account for the different pharmacological profiles of I2-imidazoline receptor subtypes.

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“…MAO proteins have molecular weights around 55 kD. However, some I 2 sites have been associated with a 29/30 kD IRBP cluster in brain 58. Correlations have been established between the immuno‐intensities of the 29/30 kD IRBP bands versus B max values for I 2 sites across several rat and human tissues and after different regulatory conditions 58.…”

Section: Brain I2 Sitesmentioning

confidence: 99%

Relevance of Imidazoline Receptors and Agmatine to Psychiatry: A Decade of Progress

Halaris

2003

Annals of the New York Academy of Sciences

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The cardiovascular relevance of imidazoline receptors (IR) has received tremendous attention since their discovery in 1984. However, evidence also has accumulated for the relevance of IR and an endogenous ligand, agmatine, to psychiatric disease. Emphasis has been placed on altered levels of the I(1)-imidazoline site on human platelets and in human postmortem brain tissue from depressed patients. Attempts at exploring the molecular nature of the I(1) protein have led to the cloning of a protein, IRAS. Based on transfection studies, IRAS seems to be involved in neuronal plasticity events. The I(2) site also appears linked to psychiatric research since some of these sites are localized to a specific domain on monoamine oxidases. Different peptides have been identified by means of an imidazoline-receptor-binding-protein (IRBP) antiserum, and these peptides, some of which appear to be fragments derived from IRAS, undergo changes in platelets and brain commensurate with altered mood states of the subject, notably depressive symptomatology. The search for an endogenous ligand for imidazoline receptor(s) also has led to agmatine, a decarboxylated derivative of arginine. Research on agmatine has mushroomed over the past several years and its measurement in the blood and brain has opened new research opportunities. This novel neurotransmitter interacts with a variety of receptors and has been implicated in mediation of stress responses, analgesia, drug addiction and withdrawal, convulsions, and neuroprotection. Given that IR and agmatine appear involved in a multitude of neurophysiologic and pathologic functions, the potential for new drug development is intriguing.

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Pharmacological modulation of immunoreactive imidazoline receptor proteins in rat brain: relationship with non‐adrenoceptor [³H]‐idazoxan binding sites

Cited by 35 publications

References 38 publications

Analysis of the Pharmacological and Molecular Heterogeneity of I₂-Imidazoline-Binding Proteins using Monoamine Oxidase-Deficient Mouse Models

Analysis of the Pharmacological and Molecular Heterogeneity of I₂-Imidazoline-Binding Proteins using Monoamine Oxidase-Deficient Mouse Models

Pharmacological and molecular discrimination of brain I2-imidazoline receptor subtypes

Relevance of Imidazoline Receptors and Agmatine to Psychiatry: A Decade of Progress

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Pharmacological modulation of immunoreactive imidazoline receptor proteins in rat brain: relationship with non‐adrenoceptor [3H]‐idazoxan binding sites

Cited by 35 publications

References 38 publications

Analysis of the Pharmacological and Molecular Heterogeneity of I2-Imidazoline-Binding Proteins using Monoamine Oxidase-Deficient Mouse Models

Analysis of the Pharmacological and Molecular Heterogeneity of I2-Imidazoline-Binding Proteins using Monoamine Oxidase-Deficient Mouse Models

Pharmacological and molecular discrimination of brain I2-imidazoline receptor subtypes

Relevance of Imidazoline Receptors and Agmatine to Psychiatry: A Decade of Progress

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Pharmacological modulation of immunoreactive imidazoline receptor proteins in rat brain: relationship with non‐adrenoceptor [³H]‐idazoxan binding sites

Analysis of the Pharmacological and Molecular Heterogeneity of I₂-Imidazoline-Binding Proteins using Monoamine Oxidase-Deficient Mouse Models

Analysis of the Pharmacological and Molecular Heterogeneity of I₂-Imidazoline-Binding Proteins using Monoamine Oxidase-Deficient Mouse Models