High affinity binding of 3H rauwolscine and 3H RX781094 to α2 adrenergic receptors and non-stereo selective sites in human and rabbit brain cortex membranes

Convents, André; Convents, D; Backer, J.-P. De; Keyser, Jacques De; Vauquelin, Georges

doi:10.1016/0006-2952(89)90385-7

Cited by 64 publications

(20 citation statements)

References 19 publications

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“…Others speculated that, due to the pres ence of a nonstereoselective adrenergic binding site, the density of az-adrenoceptors may be overestimated by this method (Convents et al 1989; Lehmann et al 1989). …”

Section: Discussionmentioning

confidence: 99%

“…This speculation was based on measurements per formed on homogenates of human and rabbit cortex (Convents et al 1989) in the presence of a buffer con siderably different and at a concentration of 3H-ida zoxan signiftcantly higher than that used in the au toradiographic procedure. The displacement curve produced by phentolamine under those conditions was shallow and biphasic, and 10 IlmollL phentolamine only displaced approximately 40% of the total binding.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Chronic Administration of Antidepressants on α2-Adrenoceptors in the Locus Coeruleus and Its Projection Fields in Rat Brain Determined by Quantitative Autoradiography

Kovachich

Frazer

Aronson

1993

Neuropsychopharmacol

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The density of a2-adrenoceptors, using 3H-idazoxan as the radioligand, was determined by quantitative lUtoradiography in the locus coeruleus and in 13 noradrenergic projection fields following chronic Idministration of drugs acting on noradrenergic and/or StTOtonergic neurons. Protriptyline, an inhibitor of the JlPfake of norepinephrine, and mianserin, an al'lUirenoceptor antagonist, reduced the binding of lH·idazoxan only in the locus coeruleus. Phenelzine, an inhibitor of both type A and type B monoamine oxidase (MAO), reduced the binding of 3H-idazoxan in the locus CM'II leus and in several areas with noradrenergic innervation from tegmental cell bodies. Clorgyline, a stltctive inhibitor of type A MAO, had no effect. Of the trro selective inhibitors of serotonin uptake, citalopram lEY WORDS: a2-adrenoceptors; 3H-Idazoxan; Locus uxruleus: Antidepressants

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of Chronic Administration of Antidepressants on α2-Adrenoceptors in the Locus Coeruleus and Its Projection Fields in Rat Brain Determined by Quantitative Autoradiography

Kovachich

Frazer

Aronson

1993

Neuropsychopharmacol

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“…Idazoxan, in addition to its ␣2-AR antagonist properties, exhibits very mild 5-HT 1A receptor agonist properties (Llado et al, 1996;Sastre-Coll et al, 1999) and also I2-imidazoline agonist properties (Convents et al, 1989). Because I2-imidazoline receptors are expressed in the striatum (Vauquelin et al, 1999) and not in STN, an alternate target could only be the inhibitory postsynaptic 5-HT 1A receptor on STN neurons (Pompeiano et al, 1994;Stanford et al, 2005).…”

Section: Effects Of ␣2 Noradrenergic Agents On Stn Neuronal Activitymentioning

confidence: 99%

Noradrenergic Modulation of Subthalamic Nucleus Activity: Behavioral and Electrophysiological Evidence in Intact and 6-Hydroxydopamine-Lesioned Rats

Belujon¹,

Bézard²,

Taupignon³

et al. 2007

J. Neurosci.

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The subthalamic nucleus (STN) plays a key role in the pathophysiology of Parkinson's disease. The modulation of the STN by norepinephrine, however, is unknown. The present study aims at characterizing the effects of systemic administration of noradrenergic agents on locomotor activity and on in vivo extracellularly recorded STN neuronal activity in intact and 6-hydroxydopamine (6-OHDA)-lesioned rats. Using selective agonists and antagonists of ␣1 and ␣2 adrenergic receptors (ARs), we show that STN neurons have functional ␣1-and ␣2-AR controlling STN firing with an impact on locomotor activity. We further demonstrate that those systemic effects are supported, at least in part, by a direct modulation of STN neuronal activity, using patch-clamp recordings of STN neurons in brain slices. These findings support the premise that hypokinesia is associated with an increased STN neuronal activity, and that improvements of parkinsonian motor abnormalities are associated with a decrease in STN activity. Our data challenge assumptions about the role of ␣1-AR and ␣2-AR in the regulation of STN neurons in both intact and 6-OHDA-lesioned rats and further ground the rationale for using ␣2-AR noradrenergic antagonists in Parkinson's disease, albeit via an unexpected mechanism.

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“…Furthermore, in some studies it was claimed that about 50% of a,-adrenoceptors in rat cerebral cortex were of the a,,type; the remaining being of the azA-type (Bylund 1985;Young et al 1989;Brown et al 1990). Besides, previous investigations have suggested that 3H-rauwolscine may bind to serotonin receptors in rat cerebral cortex (Broadhurst et al 1988;Convents et al 1989), thus complicating the interpretation of data generated by use of this ligand. However, in the studies cited above either 'H-yohimbine or 3H-rauwolscine were used to label the a,-adrenoceptors.…”

Section: Kidneymentioning

confidence: 99%

Rat Spinal Cord α₂‐Adrenoceptors are of the α_2A‐Subtype: Comparison with α_2A‐ and α_2B‐Adrenoceptors in Rat Spleen, Cerebral Cortex and Kidney Using ³H‐RX821002 Ligand Binding

Uhlén

Wikberg

1991

Pharmacology & Toxicology

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Binding of the alpha 2-adrenoceptor antagonist radioligand 3H-RX821002 was investigated in membranes from rat spinal cord, spleen, cerebral cortex and kidney. The ligand was found to bind to saturable binding sites with apparent uniform affinities within each tissue. Seven compounds, some of which have previously been reported to be selective for either alpha 2A- or alpha 2B-adrenoceptors, were used in competition with 3H-RX821002. By using computer modelling, competition curves generated for three of these compounds (ARC 239, prazosin and oxymetazoline) could be resolved into two site fits in the kidney, Kd's of the drugs being compatible with the notion that these sites corresponded to alpha 2A- and alpha 2B-adrenoceptors. Moreover, rauwolscine and yohimbine were found to be about 14 and 9-fold selective for alpha 2B-adrenoceptors in the kidney. In all other tissues studied drug competition curves were uniphasic and computer modelled into one site fits, drug Kd's being well correlated to those for the alpha 2A-adrenoceptor. In rat spinal cord 26 further drugs, which showed wide variation in structure, were evaluated in competition with 3H-RX821002. Of these compounds, competion curves of the agonists UK-14,304, (-) and (+) adrenaline were modelled into two site fits whereas those of the remaining compounds could be modelled only into one site fits. Since the high affinity site for UK-14,304, (-) and (+) adrenaline was eliminated when EDTA, Gpp(NH)p and 140 mM NaCl was present in the assay the heterogeniety observed in spinal cord was considered to be due to formation of high and low affinity conformations of the alpha 2-adrenoceptor for agonists. It is concluded that 3H-RX821002 is useful to label both alpha 2A- and alpha 2B-adrenoceptors in the rat. Moreover, the binding sites labelled by 3H-RX821002 in the spinal cord appear to consist of a single population of alpha 2-adrenoceptors of the alpha 2A-type.

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High affinity binding of 3H rauwolscine and 3H RX781094 to α2 adrenergic receptors and non-stereo selective sites in human and rabbit brain cortex membranes

Cited by 64 publications

References 19 publications

Effect of Chronic Administration of Antidepressants on α2-Adrenoceptors in the Locus Coeruleus and Its Projection Fields in Rat Brain Determined by Quantitative Autoradiography

Effect of Chronic Administration of Antidepressants on α2-Adrenoceptors in the Locus Coeruleus and Its Projection Fields in Rat Brain Determined by Quantitative Autoradiography

Noradrenergic Modulation of Subthalamic Nucleus Activity: Behavioral and Electrophysiological Evidence in Intact and 6-Hydroxydopamine-Lesioned Rats

Rat Spinal Cord α₂‐Adrenoceptors are of the α_2A‐Subtype: Comparison with α_2A‐ and α_2B‐Adrenoceptors in Rat Spleen, Cerebral Cortex and Kidney Using ³H‐RX821002 Ligand Binding

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High affinity binding of 3H rauwolscine and 3H RX781094 to α2 adrenergic receptors and non-stereo selective sites in human and rabbit brain cortex membranes

Cited by 64 publications

References 19 publications

Effect of Chronic Administration of Antidepressants on α2-Adrenoceptors in the Locus Coeruleus and Its Projection Fields in Rat Brain Determined by Quantitative Autoradiography

Effect of Chronic Administration of Antidepressants on α2-Adrenoceptors in the Locus Coeruleus and Its Projection Fields in Rat Brain Determined by Quantitative Autoradiography

Noradrenergic Modulation of Subthalamic Nucleus Activity: Behavioral and Electrophysiological Evidence in Intact and 6-Hydroxydopamine-Lesioned Rats

Rat Spinal Cord α2‐Adrenoceptors are of the α2A‐Subtype: Comparison with α2A‐ and α2B‐Adrenoceptors in Rat Spleen, Cerebral Cortex and Kidney Using 3H‐RX821002 Ligand Binding

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Rat Spinal Cord α₂‐Adrenoceptors are of the α_2A‐Subtype: Comparison with α_2A‐ and α_2B‐Adrenoceptors in Rat Spleen, Cerebral Cortex and Kidney Using ³H‐RX821002 Ligand Binding