MT9, a natural peptide from black mamba venom antagonizes the muscarinic type 2 receptor and reverses the M2R-agonist-induced relaxation in rat and human arteries

Ciolek, Justyna; Zoukimian, Claude; Dhot, J.; Burban, Mélanie; Triquigneaux, Mathilde; Lauzier, Benjamin; Guimbert, Christelle; Boturyn, Didier; Ferron, Marine; Ciccone, Lidia; Tepshi, Livia; Stura, E.A.; Legrand, Pierre; Robin, Philippe; Mourier, Gilles; Schaack, Béatrice; Fellah, Imen; Blanchet, Guillaume; Gauthier-Erfanian, Chantal; Béroud, Rémy; Servent, Denis; Waard, Michel De; Gilles, Nicolas

doi:10.1016/j.biopha.2022.113094

Cited by 3 publications

(2 citation statements)

References 48 publications

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“…Among the GPCRs-interacting toxins, Atractaspis snakes sarafotoxins activate endothelin receptors, inducing a strong general vasoconstriction leading to heart failure and cardiac arrest [41]. Finally, the M2 muscarinic toxin MT9 from the black mamba increases mesenteric artery contraction [42]. Despite the existence of many toxins with cardiovascular effects, there is only one family of toxins known to target the RAS: these are the bradykinin-potentiating peptides isolated from Brazilian pit viper which led to the development of the antihypertensive blockbuster captopril targeting ACE [43].…”

Section: Discussionmentioning

confidence: 99%

Characterization of the First Animal Toxin Acting as an Antagonist on AT1 Receptor

Baelen

Iturrioz

Chaigneau

et al. 2023

IJMS

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The renin-angiotensin system (RAS) is one of the main regulatory systems of cardiovascular homeostasis. It is mainly composed of angiotensin-converting enzyme (ACE) and angiotensin II receptors AT1 and AT2. ACE and AT1 are targets of choice for the treatment of hypertension, whereas the AT2 receptor is still not exploited due to the lack of knowledge of its physiological properties. Peptide toxins from venoms display multiple biological functions associated with varied chemical and structural properties. If Brazilian viper toxins have been described to inhibit ACE, no animal toxin is known to act on AT1/AT2 receptors. We screened a library of toxins on angiotensin II receptors with a radioligand competition binding assay. Functional characterization of the selected toxin was conducted by measuring second messenger production, G-protein activation and β-arrestin 2 recruitment using bioluminescence resonance energy transfer (BRET) based biosensors. We identified one original toxin, A-CTX-cMila, which is a 7-residues cyclic peptide from Conus miliaris with no homology sequence with known angiotensin peptides nor identified toxins, displaying a 100-fold selectivity for AT1 over AT2. This toxin shows a competitive antagonism mode of action on AT1, blocking Gαq, Gαi3, GαoA, β-arrestin 2 pathways and ERK1/2 activation. These results describe the first animal toxin active on angiotensin II receptors.

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Section: Discussionmentioning

confidence: 99%

Characterization of the First Animal Toxin Acting as an Antagonist on AT1 Receptor

Baelen

Iturrioz

Chaigneau

et al. 2023

IJMS

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“…Indeed, several GPCR toxins with original activities and promising applications have been described recently. These toxins act on the M2 muscarinic receptor implied in arterial contraction [ 80 ], on the melanocortin type 4 receptor implied in energy homeostasis [ 81 , 82 ] and on angiotensin receptors implied in cardiovascular homeostasis [ 83 ].…”

Section: Discussion Conclusion and Future Directionsmentioning

confidence: 99%

Natural Peptide Toxins as an Option for Renewed Treatment of Type 2 Vasopressin Receptor-Related Diseases

Gilles

2023

Biology

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The type 2 vasopressin receptor (V2R) is expressed in the kidneys, and it is the keystone of water homeostasis. Under the control of the antidiuretic hormone vasopressin, the V2R ensures vital functions, and any disturbance has dramatic consequences. Despite decades of research to develop drugs capable of activating or blocking V2R function to meet real medical needs, only one agonist and one antagonist are virtually used today. These two drugs cover only a small portion of patients’ needs, leaving millions of patients without treatment. Natural peptide toxins known to act selectively and at low doses on their receptor target could offer new therapeutic options.

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Biomedical applications of synthetic peptides derived from venom of animal origin: A systematic review

Díaz-Gómez,

Martín-Estal,

Rivera-Aboytes

et al. 2024

Biomedicine & Pharmacotherapy

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MT9, a natural peptide from black mamba venom antagonizes the muscarinic type 2 receptor and reverses the M2R-agonist-induced relaxation in rat and human arteries

Cited by 3 publications

References 48 publications

Characterization of the First Animal Toxin Acting as an Antagonist on AT1 Receptor

Characterization of the First Animal Toxin Acting as an Antagonist on AT1 Receptor

Natural Peptide Toxins as an Option for Renewed Treatment of Type 2 Vasopressin Receptor-Related Diseases

Biomedical applications of synthetic peptides derived from venom of animal origin: A systematic review

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