Properties of a new radioiodinated antagonist for human vasopressin V2 and V1a receptors

Ala, Y; Morin, Denis; Mahé, Eve; Cotte, Nathalie; Mouillac, Bernard; Jard, Serge; Barberis, Claude; Tribollet, Eliane; Dreifuss, Jean-Jacques; Sawyer, Wilbur H.; Wo, Nga Ching; Çhan, W. Y.; Kołodziejczyk, Aleksandra S.; Cheng, Ling; Manning, Maurice

doi:10.1016/s0014-2999(97)01021-2

Cited by 24 publications

(9 citation statements)

References 30 publications

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“…The binding curves that result can be compared to determine the ideal concentration at which a majority of binding to one receptor is displaced, but the binding to the other receptor is unaffected. For the AVPR1A competitor SR49059, whose use to selectively occupy AVPR1A in a competitive binding approach has been suggested previously (Ala et al, 1997), we determined that the best concentration for SR49059 to bind to displace 125 I-OVTA from hAVPR1A without affecting binding to hOXTR is 10 nM (Figure 1E). The OXTR antagonist ALS-II-69 is extremely selective for the human OXTR, and it only barely begins to displace 125 I-LVA from the hAVPR1A at concentrations higher than 1 μM (Figure 1F).…”

Section: Resultsmentioning

confidence: 87%

The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta)

Freeman

Inoue

Smith

et al. 2014

Psychoneuroendocrinology

173

159

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The rhesus macaque (Macaca mulatta) is an important primate model for social cognition, and recent studies have begun to explore the impact of oxytocin on social cognition and behavior. Macaques have great potential for elucidating the neural mechanisms by which oxytocin modulates social cognition, which has implications for oxytocin-based pharmacotherapies for psychiatric disorders such as autism and schizophrenia. Previous attempts to localize oxytocin receptors (OXTR) in the rhesus macaque brain have failed due to reduced selectivity of radioligands, which in primates bind to both OXTR and the structurally similar vasopressin 1a receptor (AVPR1A). We have developed a pharmacologically-informed competitive binding autoradiography protocol that selectively reveals OXTR and AVPR1A binding sites in primate brain sections. Using this protocol, we describe the neuroanatomical distribution of OXTR in the macaque. Finally, we use in situ hybridization to localize OXTR mRNA. Our results demonstrate that OXTR expression in the macaque brain is much more restricted than AVPR1A. OXTR is largely limited to the nucleus basalis of Meynert, pedunculopontine tegmental nucleus, the superficial gray layer of the superior colliculus, the trapezoid body, and the ventromedial hypothalamus. These regions are involved in a variety of functions relevant to social cognition, including modulating visual attention, processing auditory and multimodal sensory stimuli, and controlling orienting responses to visual stimuli. These results provide insights into the neural mechanisms by which oxytocin modulates social cognition and behavior in this species, which, like humans, uses vision and audition as the primary modalities for social communication.

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Section: Resultsmentioning

confidence: 87%

The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta)

Freeman

Inoue

Smith

et al. 2014

Psychoneuroendocrinology

173

159

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“…The ligand affinity values were determined either directly in saturation experiments with the radiolabeled compounds or in competition binding assays by displacement of [ Table I (parts A and B, respectively). Discrepancies between K d and K i values for a given antagonist have already been observed and could be due to the addition of iodine to the tyrosylamide residue at position 9 (20).…”

Section: Determination Of Antagonist Residues Responsible For Speciesmentioning

confidence: 95%

“…The cyclic peptide antagonists were radioiodinated at position 9 on the tyrosylamide as described previously (19,20) and were used for Scatchard analysis. Membrane preparations (3-12 g of protein) were incubated for 60 min at 30°C with increasing concentrations of these radioligands (from 100 to 3000 pM).…”

Section: Drugs-avpmentioning

confidence: 99%

Identification of Residues Responsible for the Selective Binding of Peptide Antagonists and Agonists in the V2 Vasopressin Receptor

Cotte¹,

Balestre²,

Phalipou³

et al. 1998

Journal of Biological Chemistry

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To improve our understanding of the functional architecture of G protein-coupled receptors, we have taken advantage of differences among mammalian species in ligand binding to search for the rat versus human selectivity determinants of the V2 vasopressin receptor and of its peptide ligands. Our data indicate that residue 2 of species-selective peptide antagonists such as d(CH 2 ) 5 -[DIle 2 ,Ile 4 ,Tyr-NH 2 9 ]arginine vasopressin controls their rat versus human selectivity. For species-selective agonists such as desmopressin, residues 1 and 8 modulate the binding selectivity. Among residues different between rat and human V2 receptors, those localized in the upper part of the human V2 receptor have been substituted with their rat V2 homologs. Pharmacological analysis of mutant receptors revealed that residues 202 and 304 fully control the species selectivity of the discriminating antagonists in an independent and additive manner. A third residue (position 100) is necessary to observe an equivalent phenomenon for the discriminating agonists. The substitution of these three residues does not modify the affinity of the nonselective agonists and antagonists. In conclusion, extracellular loops and the top of the transmembrane domains of V2 vasopressin receptors may provide the molecular basis for peptide ligand-binding species selectivity. Very few residues in these regions may control the binding mode of both agonists and antagonists. The arginine vasopressin (AVP)1 /oxytocin receptor family represents a suitable system to investigate structure-function relationships among G protein-coupled receptors. Indeed, all four receptor subtypes for these neurohypophyseal hormones, namely the V1a, V1b, and V2 AVP receptors and the unique oxytocin receptor, have been well characterized by pharmacological and molecular cloning studies (see Ref. 1 for review). These peptide receptors share a high primary sequence homology, but display a great diversity in their functional properties. Moreover, these receptors interact with many potent selective agonists and several classes of antagonist ligands, such as cyclic and linear peptides (2) as well as nonpeptides (3,4). By a combination of receptor three-dimensional molecular modeling and site-directed mutagenesis approaches, our preceding study has led to the mapping of the AVP agonist-binding domain in the V1a receptor subtype (5). The hormone-binding site is localized in a narrow cleft delimited by most of the transmembrane regions ϳ15 Å away from the extracellular surface. Because of the high conservation of residues involved in the interaction with the hormone, this binding site has been proposed to be common to the V1b, V2, and oxytocin receptors. An extracellular residue responsible for receptor subtype agonist selectivity has also been identified (6 -8).These first analyses did not provide much information on the definition of AVP/oxytocin receptor antagonist-binding domains. To date, only the upper part of transmembrane region VII and a hydrophobic cluster of aromatic residue...

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“…Cells were washed twice in PBS, then PBS supplemented with glucose 5.5 mM and isobutylmethylxanthine 1 mM was added for 15 min. AVP (at concentrations ranging from 10 −12 to 10 −5 M) or the V 2 receptor antagonists, SR‐121463A [30], OPC‐31260 [31], d(CH 2 ) 5 [ d ‐Tyr(Et) 2 ,Val 4 ,Tyr‐NH 2 9 ]AVP [32]and d(CH 2 ) 5 [ d ‐Ile 2 ,Ile 4 ,Tyr‐NH 2 9 ]AVP [33]were added to the medium. After a further 10 min incubation period, the reaction was stopped by replacing the incubation medium with 1 ml of 5% trichloroacetic acid.…”

Section: Methodsmentioning

confidence: 99%

The D136A mutation of the V₂ vasopressin receptor induces a constitutive activity which permits discrimination between antagonists with partial agonist and inverse agonist activities

et al. 1998

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Properties of a new radioiodinated antagonist for human vasopressin V2 and V1a receptors

Cited by 24 publications

References 30 publications

The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta)

The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta)

Identification of Residues Responsible for the Selective Binding of Peptide Antagonists and Agonists in the V2 Vasopressin Receptor

The D136A mutation of the V₂ vasopressin receptor induces a constitutive activity which permits discrimination between antagonists with partial agonist and inverse agonist activities

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Properties of a new radioiodinated antagonist for human vasopressin V2 and V1a receptors

Cited by 24 publications

References 30 publications

The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta)

The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta)

Identification of Residues Responsible for the Selective Binding of Peptide Antagonists and Agonists in the V2 Vasopressin Receptor

The D136A mutation of the V2 vasopressin receptor induces a constitutive activity which permits discrimination between antagonists with partial agonist and inverse agonist activities

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The D136A mutation of the V₂ vasopressin receptor induces a constitutive activity which permits discrimination between antagonists with partial agonist and inverse agonist activities