Bloody Kiss: Vazorelaxation Properties of Vampire Bat Saliva



    Who can be called one of the most famous classic monsters in literature and cinema? Of course, Dracula is a count from Transylvania, who is on a hemoglobin diet and is allergic to sunlight and garlic. No matter how mythical this creature may seem, it has a historical ancestor - Vlad III Tepes. The man he was hot-tempered, did not like lies and adored to impale his enemies. Such bloodiness became the main reason to attribute it to the number of "hellish offspring". But in the wild, long before the birth of Dracula, a family had long existed, whose blood addiction was a reality, and not a folklore fabrication - vampire bats.

    Now these little winged vampires do not cause us primitive fear, rather, on the contrary, a lively interest. Today, we will look at a study in which scientists studied the poison of vampire mice (yes, not only do they drink blood, they are also poisonous, but not quite literally), which can be the foundation for developing new treatments for various diseases in person Why scientists turned their gaze precisely on vampires, what makes them so special, and how these features can be applied in medicine - we will find answers to these and other questions in the report of the researchers. Go.

    Chiropterology (not to be confused with palmistry)

    Vampire bats are not even a family, but a subfamily of leaf-bearing bats, which received such an unusual name due to the presence of the majority of nasal leaflets on the muzzle.


    California leaf.

    Vampires can not boast of diversity and multiplicity of species, there are only three of them: ordinary vampires, white-winged and moray-footed.


    Cute little faces: ordinary, white-winged and fur-footed vampires (from left to right).

    Externally, vampire mice also do not inspire strong fear (unless of course you do not have chiroptophobia): the body size is not more than 9 cm, the weight is about 40 g, and the wingspan is up to 35 cm. This cannot be compared with a flying fox another representative of the squad of bats (body - 40 cm, wingspan - 1.5 m). Thank you very much for the evolution that these giants eat fruits.


    Milota: cub of flying fox.

    Vampires live in tropical and subtropical regions of Central and South America. During the daytime, they hide from the sun, and at night they are awake. It is worth noting that female vampires are very caring, as they look after their young (and the female brings only one year) about 9 months, longer than all other types of bats.

    We often hear about what bats are excellent night hunters - they are deft flyers and have echolocation. Because of their unusual food, the vampire ones do not need a powerful “radar”, but they hear perfectly well, determining the exact location of the sleeping victim through her breathing. And they run well, developing speeds of up to 1.2 m / s (4.32 km / h).

    The most striking feature of vampire mice, as we might have guessed from the name, is their diet, called hematophagy. Simply put, they feed on the blood of other animals. On a dark, dark night, a vampire mouse, finding a sleeping victim, lands on it or next to it, and then “scans” with its infrared sensor - receptors, which allow to determine the area on the body where the thinnest skin and the least hair, feathers or hair. Next, the vampire bites the skin with its sharp fangs, while the bite is almost imperceptible to the victim due to the anesthetic in the saliva.


    A little video about how vampire bats drink blood.

    So far, the summary of this little parasite is very vague: it drinks blood, possesses infrared receptors, attacks the sleeping, runs fast and also flies. This list alone is enough for script writers and writers to start making next horror films. But vampire mice are excellent mothers and very tactful, because they don’t disturb the sweet dream of their victims. But jokes aside, because it was the diet of vampire mice that attracted scientists, or rather the method of eating food.

    Vampire saliva also contains anti-coagulant enzymes that prevent blood from clotting. A vampire's dinner lasts no longer than half an hour, and his bite on the body of the victim can bleed for another 8 hours due to these enzymes. After such mosquitoes do not seem so annoying, is not it?

    It is these enzymes and their composition that became the object of attention of researchers. Therefore, we will move from zoology to biochemistry.

    Basis of research

    For a start it is worth noting that the role of the main character of this research was made by a specific type of vampire mice, namely Desmondus rotundus (ordinary vampire).

    Saliva of ordinary vampires (hereinafter referred to simply vampires) contains certain substances with anticoagulant properties that contribute to the activation of the vasodilator effect, which is accompanied by the expansion of blood vessels.


    Image No. 1

    Scientists were able to identify and analyze a chemical compound ( PCGFwhere v is a vampire) vampire venom, which in amino acid sequence is very similar to a human neuropeptide called calcitonin gene-related peptide ( CRP ). During the experiments, this peptide (PCGR) caused endothelium-independent relaxation of rat small mesenteric arteries.

    From the point of view of the vasodilator effect, the PCGD acts in much the same way as the CDG, relaxing the smooth muscles of the arterioles, which allows the vampires to feed on a continuous flow of blood from the victim's wound.
    Smooth muscles * - contractile tissue that does not have cross striation, which regulates blood flow in organs and tissues.
    Arterioles * - small arteries in front of the capillaries.
    In previous studies, it has already been discovered that vampire venom contains two very important anticoagulant toxin methods for their diet: draculine and DSPA (plasminogen activator of the salivary glands).

    Draculine is a glycoprotein that binds irreversibly to factors IXa and X and inhibits the conversion of prothrombin to thrombin, which prevents another process - the conversion of fibrinogen to fibrin. The result of this is that the blood of the vampire victim does not clot.

    Thus, vampires ensure the continuity of the flow of food (blood). In addition, the DSPA components destroy blood clots by destroying the fibrin mesh (formed on the vessels to prevent blood loss).

    Scientists note that other organisms also have similar mechanisms to prevent blood from clotting in victims. For example, mosquitoes have tachykinin-like peptides, bugs have nitrosyl hemoproteins, mosquitoes have a vasodilator acting through the PAC1 receptor, and horseflies have disintegrin, resulting in the formation of blood clots, like the venoms of some snakes.

    It is necessary to study in more detail the composition of the poison of vampire mice in order to better understand the mechanism of its action on blood vessels and blood vessels. Scientists note that PCVD is a strong vasodilator acting through the CDG1 receptor on vascular endothelial or smooth muscle cells. The researchers were able to demonstrate the successful effect of the fracturing fluid on resistant arteries by the same method as that of the multiple fracturing, but with greater selectivity.

    The results of the study


    Image number 2

    In the small mesenteric arteries of rats, PCGRP showed strong vasorelaxant properties (pEC50 = 9.47 ± 0.32 −logM, Rmax = 94.6 ± 2.4%) with ligand molar activity and efficacy as in rat calcitonin gene-related peptide (pEC50 = 9.16 ± 0.17 -logM Rmax = 93.8 ± 2.6), as shown in graph 2A .
    Rmax * - designation of maximum relaxation.
    pEC50 (−logM) * - designation of the receptor antagonist concentration, resulting in a fifty percent relaxation.
    The molar activity of the ligand * is a measure of the activity of a substance necessary to achieve the desired clinical result.
    In the presence of a rat CGRP1 receptor antagonist CGRP8-37, the molar activity of the ligand and the efficiency of the CGRP decreased by 6 times, and cKGRP (where k is rat) - 5 times. At the same time, Rmax did not change ( 2B ).


    Image No. 3

    With the introduction of 100 μM (1 μM = 10 −6 mol / l) of L-NG-nitroarginine methyl ester (L-NAME), vascular relaxation (vasodilatation) by PCGF did not change ( ). But the molar activity of the kKGRP ligand decreased by 5 times, and the maximum relaxation remained the same ( 3D ).

    Also, the cytosolic (soluble) guanylylcyclase ODQ inhibitors (10 μM) or the adenylate cyclase SQ22536 (10 μM) had no effect on the relaxation indices via PCGRP / cKGRP.


    Image No. 4

    Increasing the extracellular concentration of K + to 30 mM (1 mM = 10 −3 mol / l) noticeably weakened the relaxant effect of PCGF ( 4A ).

    The efficiency of the PCGR was reduced by a factor of 30 by blocking the voltage-dependent K + channels by 1 mM 4-aminopyridine (C 5 H 6 N 2). In this case, the introduction of 10 μM glibenclamide (an inhibitor of ATP-sensitive potassium channels) or 1 mM TEA (an inhibitor of calcium-dependent potassium channels) vasorelaxation does not change at all ( 4B ).

    To get acquainted with the details and nuances of the study I recommend to look into the report of the research group .

    Epilogue

    In the future, scientists are going to study in more detail the mechanism by which PCRP causes relaxation indirectly from the endothelium. The data from this study showed that an increase in the concentration of extracellular K + to 30 mM markedly weakens the relaxation from PCGR. This suggests the idea that this peptide modulates the relaxation of rat small mesenteric arteries in part through the activation of potassium channels.

    In the future, scientists plan to conduct similar studies with two other types of vampire bats and some kind of bats that do not feed on blood, to compare the data.

    Scientists also note that the selectivity of the effect of VCRP only on vascular smooth muscle cells can play an important role in creating new ways to combat kidney disease, hypertension, heart failure, etc.

    Understanding the details of the mechanism of vasorelaxation, which occurs through the action of certain components of the poison of vampires on certain components of the victim’s tissues, can not only play an important role in medicine, but also in understanding hematophagous organisms.

    We associate vampires with horror films, coffins for sleeping, long robes, aspen sticks and the fear of garlic. And all thanks to the art of literature and cinema. But at the same time real vampires are not so scary. And this study makes them even possible "doctors" of the future.

    And, of course, Friday offtop:

    “The last time I tell you, Ozzy is not hiding in your closet” (I will give you a hint of what exactly Ozzy is - Black Sabbath)

    Thank you for your attention, stay curious and have a great weekend, guys.

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