Vampire Venom: Vasodilatory Mechanisms of Vampire Bat (Desmodus rotundus) Blood Feeding

Abstract

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.

D. russelii Venom Mediates Vasodilatation of Resistance Like Arteries via Activation of Kv and KCa Channels

“…Cumulative concentration–response curves to venom (1 ng/mL–1 µg/mL) were constructed in vessels pre-contracted submaximally to ~50% F max with titrated concentrations of U46619 (0.01–0.2 µM). Responses to venom were obtained in endothelium-intact mesenteric arteries pre-incubated for 30 min with either 30 mM K + [45], mepyramine (0.1 µM), L-NAME (100 µM) [44], TEA (1000 µM) [46], iberiotoxin (0.1 µM), apamin (0.1 µM), TRAM-34 (1 µM), 4-aminopyridine (1000 µM) [44], glibenclamide (10 µM) [47,48] or RN-1734 (10 µM). Cumulative concentration-response curves were also constructed to venom alone (1 ng/mL–1 µg/mL) or GSK1016790A in the presence and absence of RN-1734 (10 µM).…”

An ancient, conserved gene regulatory network led to the rise of oral venom systems

“…CRISPs play a wide variety of roles in non-venomous tissues, and their function appears likewise diverse in venoms (67). Vampire bats use a calcitonin gene-related peptide (CGRP) as a vasodilator (68), and this peptide is likewise expressed in human and rat saliva, as well as other tissues (69,70). As CGRPs are potent vasodilators, their co-option into bat venom should enhance its function.…”

Spillover: the role of bats and relationships as reservoirs of zoonotic viruses and the origin of new coronaviruses

“…72 The species Desmodus rotundus has been studied due to the antithrombolysinic action of draculin presenting relaxing vessel efficacy and facilitating blood flow in vascular diseases in vivo. 73 Studies of this vampire bat-derived plasminogen activator, more recently referred to as desmoteplase, revealed that this protease has become attractive for the clinical development of patients with ischemic stroke. 74 Phylogenetic analyses, proposed by Latinne 75 show that the exchange between families and bat genera occurred more commonly in the Rhinolophidae family and in the genus Rhinolophus, host exchanges were more frequent and in host letons in alpha-CoVs and beta-CoVs, presenting a probable origin for SARS-CoV-2 in Rhinolophus spp bats.…”