{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:48:57Z","timestamp":1790650137169,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,8]],"date-time":"2019-01-08T00:00:00Z","timestamp":1546905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Animals that specialise in blood feeding have particular challenges in obtaining their meal, whereby they impair blood hemostasis by promoting anticoagulation and vasodilation in order to facilitate feeding. These convergent selection pressures have been studied in a number of lineages, ranging from fleas to leeches. However, the vampire bat (Desmondus rotundus) is unstudied in regards to potential vasodilatory mechanisms of their feeding secretions (which are a type of venom). This is despite the intense investigations of their anticoagulant properties which have demonstrated that D. rotundus venom contains strong anticoagulant and proteolytic activities which delay the formation of blood clots and interfere with the blood coagulation cascade. In this study, we identified and tested a compound from D. rotundus venom that is similar in size and amino acid sequence to human calcitonin gene-related peptide (CGRP) which has potent vasodilatory properties. We found that the vampire bat-derived form of CGRP (i.e., vCGRP) selectively caused endothelium-independent relaxation of pre-contracted rat small mesenteric arteries. The vasorelaxant efficacy and potency of vCGRP were similar to that of CGRP, in activating CGRP receptors and Kv channels to relax arteriole smooth muscle, which would facilitate blood meal feeding by promoting continual blood flow. Our results provide, for the first time, a detailed investigation into the identification and function of a vasodilatory peptide found in D. rotundus venom, which provides a basis in understanding the convergent pathways and selectivity of hematophagous venoms. These unique peptides also show excellent drug design and development potential, thus highlighting the social and economic value of venomous animals.<\/jats:p>","DOI":"10.3390\/toxins11010026","type":"journal-article","created":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T03:06:06Z","timestamp":1547003166000},"page":"26","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Vampire Venom: Vasodilatory Mechanisms of Vampire Bat (Desmodus rotundus) Blood Feeding"],"prefix":"10.3390","volume":"11","author":[{"given":"Rahini","family":"Kakumanu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing &amp; Health Sciences, Monash University, Clayton, Victoria 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne C.","family":"Hodgson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing &amp; Health Sciences, Monash University, Clayton, Victoria 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravina","family":"Ravi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing &amp; Health Sciences, Monash University, Clayton, Victoria 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Alagon","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Av. Universidad 2001, Cuernavaca, Morelos 62210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4412-2275","authenticated-orcid":false,"given":"Richard J.","family":"Harris","sequence":"additional","affiliation":[{"name":"Venom Evolution Lab, School of Biological Sciences, University of Queensland, St. Lucia, Queensland 4067, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Brust","sequence":"additional","affiliation":[{"name":"Institute for Molecular Biosciences, University of Queensland, St Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul F.","family":"Alewood","sequence":"additional","affiliation":[{"name":"Institute for Molecular Biosciences, University of Queensland, St Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara K.","family":"Kemp-Harper","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing &amp; Health Sciences, Monash University, Clayton, Victoria 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6661-1283","authenticated-orcid":false,"given":"Bryan G.","family":"Fry","sequence":"additional","affiliation":[{"name":"Venom Evolution Lab, School of Biological Sciences, University of Queensland, St. Lucia, Queensland 4067, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Greenhall, A.M. (2018). Natural History of Vampire Bats, CRC Press.","DOI":"10.1201\/9781351074919"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.tree.2012.10.020","article-title":"Complex cocktails: The evolutionary novelty of venoms","volume":"28","author":"Casewell","year":"2013","journal-title":"Trends Ecol. Evol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/0167-5877(92)90080-Y","article-title":"Relative population densities and predation of the common vampire bat (Desmodus rotundus) in natural and cattle-raising areas in north-east argentina","volume":"14","author":"Delpietro","year":"1992","journal-title":"Prev. Vet. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/jmor.1051060305","article-title":"Anatomy and histochemistry of the salivary glands of the vampire bat, Desmodus rotundus murinus","volume":"106","author":"Disanto","year":"1960","journal-title":"J. Morphol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0304-4165(98)00082-8","article-title":"Expression of biological activity of draculin, the anticoagulant factor from vampire bat saliva, is strictly dependent on the appropriate glycosylation of the native molecule","volume":"1425","author":"Fernandez","year":"1998","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0167-4838(99)00160-0","article-title":"Draculin, the anticoagulant factor in vampire bat saliva, is a tight-binding, noncompetitive inhibitor of activated factor X","volume":"1434","author":"Fernandez","year":"1999","journal-title":"Biochim. Biophys. Acta Protein Struct. Mol. Enzym."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1055\/s-0038-1653731","article-title":"Purification and partial characterization of draculin, the anticoagulant factor present in the saliva of vampire bats (Desmodus rotundus)","volume":"73","author":"Beguin","year":"1995","journal-title":"Thromb. Haemost."},{"key":"ref_8","first-page":"219","article-title":"An outbreak of vampire bat bite in a Brazilian village","volume":"44","author":"Bonito","year":"1993","journal-title":"Trop. Med. Parasitol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1590\/S0102-311X2001000600025","article-title":"Common vampire bat attacks on humans in a village of the amazon region of Brazil","volume":"17","author":"Schneider","year":"2001","journal-title":"Cadernos Sa\u00fade P\u00fablica"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1590\/S1020-49892009000300010","article-title":"Rabies transmitted by vampire bats to humans: An emerging zoonotic disease in Latin America?","volume":"25","author":"Schneider","year":"2009","journal-title":"Revista Panamericana Salud P\u00fablica"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"320","DOI":"10.4269\/ajtmh.1989.40.320","article-title":"Human depredation by vampire bats (Desmodus rotundus) following a hog cholera campaign","volume":"40","author":"McCarthy","year":"1989","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_12","unstructured":"Constantine, D.G. (1970). Bats in Relation to the Health Welfare and Economy of Man, Academic Press Incorporated."},{"key":"ref_13","first-page":"143","article-title":"Vascular\u2013platelet and plasma hemostasis regulators from bloodsucking animals","volume":"67","author":"Basanova","year":"2002","journal-title":"Biochemistry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00114-008-0446-0","article-title":"Keeping the blood flowing\u2014Plasminogen activator genes and feeding behavior in vampire bats","volume":"96","author":"Dittmar","year":"2009","journal-title":"Naturwissenschaften"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/211434c0","article-title":"Plasminogen activator in saliva of the vampire bat Desmodus rotundus","volume":"211","author":"Hawkey","year":"1966","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1111\/j.1365-2141.1967.tb08870.x","article-title":"Inhibitor of platelet aggregation present in saliva of the vampire bat Desmodus rotundus","volume":"13","author":"Hawkey","year":"1967","journal-title":"Br. J. Haematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1073\/pnas.91.1.138","article-title":"Sialokinin I and II: Vasodilatory tachykinins from the yellow fever mosquito Aedes aegypti","volume":"91","author":"Champagne","year":"1994","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1093\/jmedent\/31.5.747","article-title":"Salivary vasodilators of Aedes triseriatus and Anopheles gambiae (Diptera: Culicidae)","volume":"31","author":"Ribeiro","year":"1994","journal-title":"J. Med. \u00c8ntomol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1242\/jeb.198.5.1093","article-title":"Nitric oxide loading of the salivary nitric-oxide-carrying hemoproteins (nitrophorins) in the blood-sucking bug Rhodnius prolixus","volume":"198","author":"Nussenzveig","year":"1995","journal-title":"J. Exp. Boil."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1242\/jeb.198.7.1519","article-title":"A salivary nitrophorin (nitric-oxide-carrying hemoprotein) in the bedbug Cimex lectularius","volume":"198","author":"Valenzuela","year":"1995","journal-title":"J. Exp. Boil."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1016\/j.peptides.2007.06.021","article-title":"Maxadilan, a PAC1 receptor agonist from sand flies","volume":"28","author":"Lerner","year":"2007","journal-title":"Peptides"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11234","DOI":"10.1016\/S0021-9258(18)99153-2","article-title":"Isolation of maxadilan, a potent vasodilatory peptide from the salivary glands of the sand fly Lutzomyia longipalpis","volume":"266","author":"Lerner","year":"1991","journal-title":"J. Boil. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1160\/TH11-01-0029","article-title":"A novel family of RGD-containing disintegrin (Tablysin-15) from the salivary gland of the horsefly Tabanus yao targets integrins \u03b1IIb\u03b23 and \u03b1v\u03b23 and inhibits platelet aggregation and angiogenesis","volume":"105","author":"Ma","year":"2011","journal-title":"Thromb. Haemost."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1081\/TXR-200057848","article-title":"Bioactive compounds in tick and mite venoms (saliva)","volume":"24","author":"Tu","year":"2005","journal-title":"Toxin Rev."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Greenhall, A.M. (1988). Feeding behavior. Nat. Hist. Vampire Bats, 111\u2013131.","DOI":"10.1201\/9781351074919-9"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jprot.2013.05.034","article-title":"Dracula\u2019s children: Molecular evolution of vampire bat venom","volume":"89","author":"Low","year":"2013","journal-title":"J. Proteom."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/335164a0","article-title":"Calcitonin gene-related peptide acts as a novel vasodilator neurotransmitter in mesenteric resistance vessels of the rat","volume":"335","author":"Kawasaki","year":"1988","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/j.1365-2125.1987.tb03154.x","article-title":"The actions of calcitonin gene related peptide and vasoactive intestinal peptide as vasodilators in man in vivo and in vitro","volume":"24","author":"Thom","year":"1987","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/0014-5793(86)81091-2","article-title":"Structure and expression of the human calcitonin\/CGRP genes","volume":"209","author":"Steenbergh","year":"1986","journal-title":"FEBS Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/304129a0","article-title":"Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing","volume":"304","author":"Rosenfeld","year":"1983","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1152\/physrev.00034.2013","article-title":"Calcitonin gene-related peptide: Physiology and pathophysiology","volume":"94","author":"Russell","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1111\/j.1600-0773.1994.tb01087.x","article-title":"Characterization of the CGRP receptor and mechanisms of action in rat mesenteric small arteries","volume":"74","author":"Lei","year":"1994","journal-title":"Pharmacol. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1167\/iovs.04-1093","article-title":"The vasorelaxing effect of CGRP and natriuretic peptides in isolated bovine retinal arteries","volume":"46","author":"Boussery","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1007\/BF00164880","article-title":"Vasodilating effects of human and rat calcitonin gene-related peptides in isolated porcine coronary arteries","volume":"336","author":"Shoji","year":"1987","journal-title":"Naunyn-Schmiedebergs Arch. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1152\/physrev.00037.2003","article-title":"Vascular actions of calcitonin gene-related peptide and adrenomedullin","volume":"84","author":"Brain","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1111\/j.1476-5381.1992.tb14508.x","article-title":"Human \u03b1-calcitonin gene-related peptide stimulates adenylate cyclase and guanylate cyclase and relaxes rat thoracic aorta by releasing nitric oxide","volume":"107","author":"Gray","year":"1992","journal-title":"Br. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1111\/j.1476-5381.2012.02129.x","article-title":"Endosomal proteolysis regulates calcitonin gene-related peptide responses in mesenteric arteries","volume":"167","author":"McNeish","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/j.1748-1716.1995.tb09972.x","article-title":"Regional differences in endothelium-dependent relaxation in the rat: Contribution of nitric oxide and nitric oxide-independent mechanisms","volume":"155","author":"Zygmunt","year":"1995","journal-title":"Acta Physiol. Scand."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/344770a0","article-title":"Arterial dilations in response to calcitonin gene-related peptide involve activation of K+ channels","volume":"344","author":"Nelson","year":"1990","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1113\/jphysiol.1994.sp020045","article-title":"Calcitonin gene-related peptide activated ATP-sensitive K+ currents in rabbit arterial smooth muscle via protein kinase A","volume":"475","author":"Quayle","year":"1994","journal-title":"J. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1007\/s00424-012-1083-1","article-title":"Influence of methanandamide and CGRP on potassium currents in smooth muscle cells of small mesenteric arteries","volume":"463","author":"Bol","year":"2012","journal-title":"Pfl\u00fcgers Arch. Eur. J. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1146\/annurev.genom.9.081307.164356","article-title":"The toxicogenomic multiverse: Convergent recruitment of proteins into animal venoms","volume":"10","author":"Fry","year":"2009","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1101\/gr.3228405","article-title":"From genome to \u201cvenome\u201d: Molecular origin and evolution of the snake venom proteome inferred from phylogenetic analysis of toxin sequences and related body proteins","volume":"15","author":"Fry","year":"2005","journal-title":"Genome Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1161\/CIRCULATIONAHA.117.028388","article-title":"A novel \u03b1-calcitonin gene-related peptide analogue protects against end-organ damage in experimental hypertension, cardiac hypertrophy, and heart failureclinical perspective","volume":"136","author":"Aubdool","year":"2017","journal-title":"Circulation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.peptides.2013.07.002","article-title":"Functional characterization on invertebrate and vertebrate tissues of tachykinin peptides from octopus venoms","volume":"47","author":"Ruder","year":"2013","journal-title":"Peptides"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1111\/j.1476-5381.2009.00150.x","article-title":"A role for nitroxyl (HNO) as an endothelium-derived relaxing and hyperpolarizing factor in resistance arteries","volume":"157","author":"Andrews","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1089\/ars.2010.3279","article-title":"A novel role for HNO in local and spreading vasodilatation in rat mesenteric resistance arteries","volume":"14","author":"Yuill","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1124\/jpet.106.101790","article-title":"Endothelium-independent relaxation by adrenomedullin in pregnant rat mesenteric artery: Role of camp-dependent protein kinase a and calcium-activated potassium channels","volume":"317","author":"Ross","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1046\/j.0953-816x.2001.01688.x","article-title":"Cloning, characterization and central nervous system distribution of receptor activity modifying proteins in the rat","volume":"14","author":"Oliver","year":"2001","journal-title":"Eur. J. Neurosci."},{"key":"ref_50","first-page":"1086","article-title":"Functional calcitonin gene-related peptide subtype 2 receptors in porcine coronary arteries are identified as calcitonin gene-related peptide subtype 1 receptors by radioligand binding and reverse transcription-polymerase chain reaction","volume":"299","author":"Rorabaugh","year":"2001","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"24321","DOI":"10.1074\/jbc.271.40.24321","article-title":"A novel sulfonylurea receptor forms with BIR (Kir6. 2) a smooth muscle type ATP-sensitive K+ channel","volume":"271","author":"Isomoto","year":"1996","journal-title":"J. Boil. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"H1274","DOI":"10.1152\/ajpheart.00008.2009","article-title":"Redox variants of NO (NO\u00b7 and HNO) elicit vasorelaxation of resistance arteries via distinct mechanisms","volume":"296","author":"Favaloro","year":"2009","journal-title":"Am. J. Physiol. Heart Circ. Physiol."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/1\/26\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:24:17Z","timestamp":1760185457000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/1\/26"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,8]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,1]]}},"alternative-id":["toxins11010026"],"URL":"https:\/\/doi.org\/10.3390\/toxins11010026","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,8]]}}}