Vasotocin and the origins of the vasopressin/oxytocin receptor gene family

Mayasich, Sally A.; Clarke, Benjamin L.

doi:10.1016/bs.vh.2019.08.018

Cited by 8 publications

(6 citation statements)

References 53 publications

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“…Amino acid alignments of V1A1 and V1A2 ( Figure S1 ) clearly showed a high conservation of putative AVT ligand binding sites previously identified in different studies [ 44 ], which assumes common AVT/IT binding sites between the two paralogs. A high conservation of amino acids involved in the oxytocin ligand selectivity, binding and signaling was observed within ITR and also AVTR sequences.…”

Section: Discussionsupporting

confidence: 58%

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Hypo-Osmoregulatory Roles of Vasotocinergic and Isotocinergic Systems in the Intestines of Two European Sea Bass Lineages

Cao

Blondeau‐Bidet

Lorin‐Nebel

2022

IJMS

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European sea bass (Dicentrarchus labrax) are a major aquaculture species that live in habitats with fluctuating salinities that are sometimes higher than in seawater (SW). Atlantic and West-Mediterranean genetic lineages were compared regarding intestinal neuropeptide receptor expression in SW (36%) and following a two-week transfer to hypersalinity (HW, 55%). Phylogenetic analysis revealed seven neuropeptide receptors belonging to the arginine vasotocine (AVTR) family and two isotocin receptors (ITR). Among AVTR paralogs, the highest mRNA levels were recorded for v1a2, with a two- to fourfold upregulation in the European sea bass intestinal sections after transfer of fish to HW. Principal component analysis in posterior intestines showed that v1a2 expression grouped together with the expression and activity of main ion transporters and channels involved in solute-coupled water uptake, indicating a possible role of this receptor in triggering water absorption. v1a1 expression, however, was decreased or did not change after transfer to hypersaline water. Among ITR paralogs, itr1 was the most expressed paralog in the intestine and opposite expression patterns were observed following salinity transfer, comparing intestinal sections. Overall, different expression profiles were observed between genetic lineages for several analyzed genes which could contribute to different osmotic stress-related responses in D. labrax lineages.

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Section: Discussionsupporting

confidence: 58%

“…Multiple amino-acid alignments were performed using the Geneious alignment tools and functional domain regions were identified based on Mayasich and Clarke, (2020) [ 44 ]. Sequence logos were created for the functional domain regions in AVT V1A-type receptors (V1A1 and V1A2) and ITR1 using WebLogo Version 3 ( ).…”

Section: Methodsmentioning

confidence: 99%

Hypo-Osmoregulatory Roles of Vasotocinergic and Isotocinergic Systems in the Intestines of Two European Sea Bass Lineages

Cao

Blondeau‐Bidet

Lorin‐Nebel

2022

IJMS

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“…One study concluded that the analyses supported one WGD event that was followed by "chromosomal or segmental duplications and translocations" in the jawed vertebrate lineage (13). This conclusion was repeated more recently in a book chapter from the same group (14). However, their analyses did not include neighboring gene families.…”

Section: Do Recent Studies Refute the 1r/2r Scenario Of Otr/vtr Evolu...mentioning

confidence: 99%

“…One study that also included lamprey OTR/VTR sequences concluded that the analyses supported one WGD event that was followed by "chromosomal or segmental duplications and translocations" in the jawed vertebrate lineage (13). This conclusion was repeated more recently in a book chapter from the same group (14). The most recent report on the evolution of OTR/VTR genes favored one WGD event followed by large segmental duplications (4).…”

Section: Introductionmentioning

confidence: 96%

The Evolution of Oxytocin and Vasotocin Receptor Genes in Jawed Vertebrates: A Clear Case for Gene Duplications Through Ancestral Whole-Genome Duplications

2022

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The neuronal and neuroendocrine peptides oxytocin (OT) and vasotocin (VT), including vasopressins, have six cognate receptors encoded by six receptor subtype genes in jawed vertebrates. The peptides elicit a broad range of responses that are specifically mediated by the receptor subtypes including neuronal functions regulating behavior and hormonal actions on reproduction and water/electrolyte balance. Previously, we have demonstrated that these six receptor subtype genes, which we designated VTR1A, VTR1B, OTR, VTR2A, VTR2B and VTR2C, arose from a syntenic ancestral gene pair, one VTR1/OTR ancestor and one VTR2 ancestor, through the early vertebrate whole-genome duplications (WGD) called 1R and 2R. This was supported by both phylogenetic and chromosomal conserved synteny data. More recently, other studies have focused on confounding factors, such as the OTR/VTR orthologs in cyclostomes, to question this scenario for the origin of the OTR/VTR gene family; proposing instead less parsimonious interpretations involving only one WGD followed by complex series of chromosomal or segmental duplications. Here, we have updated the phylogeny of the OTR/VTR gene family, including a larger number of vertebrate species, and revisited seven representative neighboring gene families from our previous conserved synteny analyses, adding chromosomal information from newer high-coverage genome assemblies from species that occupy key phylogenetic positions: the polypteriform fish reedfish (Erpetoichthys calabaricus), the cartilaginous fish thorny skate (Amblyraja radiata) and a more recent high-quality assembly of the Western clawed frog (Xenopus tropicalis) genome. Our analyses once again add strong support for four-fold symmetry, i.e., chromosome quadruplication in the same time window as the WGD events early in vertebrate evolution, prior to the jawed vertebrate radiation. Thus, the evolution of the OTR/VTR gene family can be most parsimoniously explained by two WGD events giving rise to the six ancestral genes, followed by differential gene losses of VTR2 genes in different lineages. We also argue for more coherence and clarity in the nomenclature of OT/VT receptors, based on the most parsimonious scenario.

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“…The V 2 R receptor is well-established as a member of the vasopressin/oxytocin receptor subfamily within the G-protein-coupled receptor superfamily, which encompasses four closely related receptor subtypes: V 1A , V 1B , V 2 , and oxytocin receptors. , This subfamily plays critical roles in the regulation of diverse physiological processes, including water homeostasis, blood pressure modulation, and social behavior, with each subtype exhibiting distinct tissue distribution and functional specificity. , Next, we examined whether compound 33 could act on other vasopressin receptor subtypes. Because V 1A and V 2 receptors are expressed in the kidney, we examined the selectivity of peptide 33 binding to the V 2 R over the V 1A receptor.…”

Section: Resultsmentioning

confidence: 99%

Long-Residence Time Peptide Antagonist for the Vasopressin V₂ Receptor to Treat Autosomal Dominant Polycystic Kidney Disease

Xiong,

Wang,

Zhang

et al. 2024

J. Med. Chem.

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The dysregulated intracellular cAMP in the kidneys drives cystogenesis and progression in autosomal dominant polycystic kidney disease (ADPKD). Mounting evidence supports that vasopressin V2 receptor (V2R) antagonism effectively reduces cAMP levels, validating this receptor as a therapeutic target. Tolvaptan, an FDA-approved V2R antagonist, shows limitations in its clinical efficacy for ADPKD treatment. Therefore, the pursuit of better-in-class V2R antagonists with an improved efficacy remains pressing. Herein, we synthesized a set of peptide V2R antagonists. Peptide 33 exhibited a high binding affinity for the V2R (K i = 6.1 ± 1.5 nM) and an extended residence time of 20 ± 1 min, 2-fold that of tolvaptan. This prolonged interaction translated into sustained suppression of cAMP production in washout experiments. Furthermore, peptide 33 exhibited improved efficacies over tolvaptan in both ex vivo and in vivo models of ADPKD, underscoring its potential as a promising lead compound for the treatment of ADPKD.

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Vasotocin and the origins of the vasopressin/oxytocin receptor gene family

Cited by 8 publications

References 53 publications

Hypo-Osmoregulatory Roles of Vasotocinergic and Isotocinergic Systems in the Intestines of Two European Sea Bass Lineages

Hypo-Osmoregulatory Roles of Vasotocinergic and Isotocinergic Systems in the Intestines of Two European Sea Bass Lineages

The Evolution of Oxytocin and Vasotocin Receptor Genes in Jawed Vertebrates: A Clear Case for Gene Duplications Through Ancestral Whole-Genome Duplications

Long-Residence Time Peptide Antagonist for the Vasopressin V₂ Receptor to Treat Autosomal Dominant Polycystic Kidney Disease

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Vasotocin and the origins of the vasopressin/oxytocin receptor gene family

Cited by 8 publications

References 53 publications

Hypo-Osmoregulatory Roles of Vasotocinergic and Isotocinergic Systems in the Intestines of Two European Sea Bass Lineages

Hypo-Osmoregulatory Roles of Vasotocinergic and Isotocinergic Systems in the Intestines of Two European Sea Bass Lineages

The Evolution of Oxytocin and Vasotocin Receptor Genes in Jawed Vertebrates: A Clear Case for Gene Duplications Through Ancestral Whole-Genome Duplications

Long-Residence Time Peptide Antagonist for the Vasopressin V2 Receptor to Treat Autosomal Dominant Polycystic Kidney Disease

Contact Info

Product

Resources

About

Long-Residence Time Peptide Antagonist for the Vasopressin V₂ Receptor to Treat Autosomal Dominant Polycystic Kidney Disease