Molecular pharmacology of AVP and OT receptors and therapeutic potential

Barberis, Claude; Morin, Didier; Durroux, Thierry; Mouillac, Bernard; Guillon, Gilles; Seyer, René; Hibert, Marcel; Tribollet, Eliane; Manning, Maurice

doi:10.1358/dnp.1999.12.5.863621

Cited by 72 publications

(113 citation statements)

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“…Since OT/vasopressin analogues bind to and activate four different receptor subtypes (OTR, V1a, V1b and V2) (Chini et al, 1995b;Peter et al, 1995;Barberis et al, 1999), peptides of potential clinical use should be checked for their receptor selectivity. Our competition experiments on receptor-rich membrane preparations showed that dLVT binds to human OTR, V1a, V1b and V2 with a pharmacological profile that is very similar to that of OT.…”

Section: Discussionmentioning

confidence: 99%

“…OT/AVP analogues bind to and activate (albeit with different affinities and efficacies) all members of the OT/AVP receptor family, which includes the OTR and the three vasopressin receptor subtypes V1a, V1b and V2 (Peter et al, 1995;Chini et al, 1995b;Barberis et al, 1999). When developing a specific OTR analogue, it is therefore essential to check its binding properties not only on the human OTR, but also on the V1a, V1b and V2 subtypes.…”

Section: Receptor Selectivitymentioning

confidence: 99%

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Improved radiotracing of oxytocin receptor-expressing tumours using the new [111In]-DOTA-Lys8-deamino-vasotocin analogue

et al. 2003

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Oxytocin receptors (OTR) have been described in a number of tumours of different origin, and represent a new target for specific radiolabelled oxytocin (OT) analogues in cancer diagnosis and therapy. By linking the DOTA chelating agent to position 8 of the deamino derivative of Lys 8 -vasotocin (dLVT), we obtained a new compound (DOTA-dLVT) with the following characteristics: (1) it forms a monomeric and stable compound that binds to OTR with an affinity comparable to that of the endogenous OT ligand; (2) it is characterised by a very good selectivity profile for the human OTR, with a low affinity binding to the closely related V1a, V1b and V2 vasopressin receptor subtypes; (3) it induces rapid and persistent receptor internalisation and (4) when radiolabelled, [ 111 In]-DOTA-dLVT is efficiently and selectively taken up by OTR-positive tumours grown in mice. These features makes radiolabelled DOTA-dLVT a very good candidate for the radiotargeting of OTR-expressing tumours.

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Section: Discussionmentioning

confidence: 99%

Section: Receptor Selectivitymentioning

confidence: 99%

Improved radiotracing of oxytocin receptor-expressing tumours using the new [111In]-DOTA-Lys8-deamino-vasotocin analogue

et al. 2003

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“…The development of specific agonists and antagonists for Avp receptors has allowed for a better elucidation of its contributions to physiology and behavior (Manning and Sawyer, 1991;Barberis et al, 1999;Serradeil-Le Gal et al, 2002a). Anatomical, pharmacological and transgenic, including "knockout," animal studies, have implicated Avp in the regulation of various social behaviors across species.…”

Section: Introductionmentioning

confidence: 99%

Vasopressin: Behavioral roles of an “original” neuropeptide

Caldwell

Lee

Macbeth

et al. 2008

Progress in Neurobiology

419

416

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Vasopressin (Avp) is mainly synthesized in the magnocellular cells of the hypothalamic supraoptic (SON) and paraventricular nuclei (PVN) whose axons project to the posterior pituitary. Avp is then released into the blood stream upon appropriate stimulation (e.g., hemorrhage or dehydration) to act at the kidneys and blood vessels. The brain also contains several populations of smaller, parvocellular neurons whose projections remain within the brain. These populations are located within the PVN, bed nucleus of the stria terminalis (BNST), medial amygdala (MeA) and suprachiasmatic nucleus (SCN).Since the 1950's, research examining the roles of Avp in the brain and periphery has intensified. The development of specific agonists and antagonists for Avp receptors has allowed for a better elucidation of its contributions to physiology and behavior. Anatomical, pharmacological and transgenic, including "knockout," animal studies, have implicated Avp in the regulation of various social behaviors across species.Avp plays a prominent role in the regulation of aggression, generally of facilitating or promoting it. Affiliation and certain aspects of pair-bonding are also influenced by Avp. Memory, one of the first brain functions of Avp that was investigated, has been implicated especially strongly in social recognition. The roles of Avp in stress, anxiety, and depressive states are areas of active exploration. In this review, we concentrate on the scientific progress that has been made on understanding the role of Avp in regulating of these and other behaviors across species, as well as discuss the implications for human behavior.

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“…Central oxytocin (OT) and vasopressin (AVP) effects are mediated by three G-protein-coupled receptors (GPCRs) that are evolutionarily highly conserved and closely related, with overall homology varying from 40 to 85%: the vasopressin 1a receptor (V1aR), the vasopressin 1b receptor (V1bR), and the OT receptor (OTR) (Barberis et al, 1999;Birnbaumer, 2000;Zingg and Laporte, 2003). OT and AVP are also structurally very similar, differing by only two amino acids in most mammals (Wallis, 2012).…”

Section: Introductionmentioning

confidence: 99%

Selective and Potent Agonists and Antagonists for Investigating the Role of Mouse Oxytocin Receptors

Busnelli

Bulgheroni

Manning

et al. 2013

J Pharmacol Exp Ther

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The neuropeptides oxytocin (OT) and vasopressin (AVP) have been shown to play a central role in social behaviors; as a consequence, they have been recognized as potential drugs to treat neurodevelopmental and psychiatric disorders characterized by impaired social interactions. However, despite the basic and preclinical relevance of mouse strains carrying genetic alterations in the OT/AVP systems to basic and preclinical translational neuroscience, the pharmacological profile of mouse OT/AVP receptor subtypes has not been fully characterized. To fill in this gap, we have characterized a number of OT and AVP agonists and antagonists at three murine OT/AVP receptors expressed in the nervous system as follows: the oxytocin (mOTR) and vasopressin V1a (mV1aR) and V1b (mV1bR) subtypes. These three receptors were transiently expressed in vitro for binding and intracellular signaling assays, and then a homology model of the mOTR structure was constructed to investigate how its molecular features compare with human and rat OTR orthologs. Our data indicate that the selectivity profile of the natural ligands, OT and AVP, is conserved in humans, rats, and mice. Furthermore, we found that the synthetic peptide [Thr 4 Gly 7 ]OT (TGOT) is remarkably selective for the mOTR and, like the endogenous OT ligand, activates G q and G i and recruits b-arrestins. Finally, we report three antagonists that exhibit remarkably high affinities and selectivities at mOTRs. These highly selective pharmacological tools will contribute to the investigation of the specific physiologic and pathologic roles of mOTR for the development of selective OT-based therapeutics.

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Molecular pharmacology of AVP and OT receptors and therapeutic potential

Cited by 72 publications

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Improved radiotracing of oxytocin receptor-expressing tumours using the new [111In]-DOTA-Lys8-deamino-vasotocin analogue

Improved radiotracing of oxytocin receptor-expressing tumours using the new [111In]-DOTA-Lys8-deamino-vasotocin analogue

Vasopressin: Behavioral roles of an “original” neuropeptide

Selective and Potent Agonists and Antagonists for Investigating the Role of Mouse Oxytocin Receptors

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