9hb3

Structural highlights

Function

MAMB1_DENAN Selectively interacts with vasopressin V2 receptor (V2R/AVPR2) and fully inhibits three major signaling pathways of this receptor that are GalphaS protein, the interaction with beta-arrestin and activation of MAP kinase (PubMed:28630289, PubMed:35122240). Inhibits vasopressin binding human V2R in the nanomolar range (Ki=5.02 nM), and also potently inhibits vasopressin-induced cAMP production (IC(50)=94 nM) (PubMed:35122240). In vivo, this protein shows an aquaretic effect (PubMed:28630289, PubMed:35122240). Urine output increases and urine osmolality decreases dramatically under treatment with this protein, without differences observed between healthy mice and the pcy mice model of the autosomal-dominant polycystic kidney disease (ADPKD) (PubMed:28630289). This protein does not modify electrolyte, protein and urea excretions in the urine samples, but produces a 3-fold decrease of creatinine levels (PubMed:28630289). Intraperitoneal injection of this protein into the pcy mice significantly reduces the number of renal cysts and the total area of cysts (PubMed:28630289). This protein also shows high efficacy in preventing hyponatremia in rat models (induced by DAVP) (PubMed:33052234). Is highly visible in mice liver and kidney after intravenous injection (PubMed:33052234). Is rapidly eliminated in the liver, whereas it exhibits slow elimination in the kidney due to the high expression of V2R which acts as a reservoir (PubMed:33052234). In addition, its elimination from blood is rapid (PubMed:33052234). Fluorescent MQ1 probes could also be used for imaging V2R-overexpressing cancer cells; note that these probes label the three renal cancer cell lines CAKI-2, ACHN and A498 that highly express V2R (PubMed:33052234). In vivo, does not show any toxicity on animals, even at highest doses tested, such as prostration, spidy coat, appetite or weight loss (PubMed:33052234).^{[1] [2] [3]}

References

1. ↑ Ciolek J, Reinfrank H, Quinton L, Viengchareun S, Stura EA, Vera L, Sigismeau S, Mouillac B, Orcel H, Peigneur S, Tytgat J, Droctove L, Beau F, Nevoux J, Lombes M, Mourier G, De Pauw E, Servent D, Mendre C, Witzgall R, Gilles N. Green mamba peptide targets type-2 vasopressin receptor against polycystic kidney disease. Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):7154-7159. doi:, 10.1073/pnas.1620454114. Epub 2017 Jun 19. PMID:28630289 doi:http://dx.doi.org/10.1073/pnas.1620454114
2. ↑ Droctové L, Lancien M, Tran VL, Susset M, Jego B, Theodoro F, Kessler P, Mourier G, Robin P, Diarra SS, Palea S, Flahault A, Chorfa A, Corbani M, Llorens-Cortes C, Mouillac B, Mendre C, Pruvost A, Servent D, Truillet C, Gilles N. A snake toxin as a theranostic agent for the type 2 vasopressin receptor. Theranostics. 2020 Sep 18;10(25):11580-11594. PMID:33052234 doi:10.7150/thno.47485
3. ↑ Droctové L, Ciolek J, Mendre C, Chorfa A, Huerta P, Carvalho C, Gouin C, Lancien M, Stanajic-Petrovic G, Braco L, Blanchet G, Upert G, De Pauw G, Barbe P, Keck M, Mourier G, Mouillac B, Denis S, Rodríguez de la Vega RC, Quinton L, Gilles N. A new Kunitz-type snake toxin family associated with an original mode of interaction with the vasopressin 2 receptor. Br J Pharmacol. 2022 Jul;179(13):3470-3481. PMID:35122240 doi:10.1111/bph.15814