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Effects of the Heterodimeric Neurotoxic Phospholipase A<sub>2</sub> from the Venom of <i>Vipera nikolskii</i> on the Contractility of Rat Papillary Muscles and Thoracic Aortas
oleh: Alexey Averin, Vladislav Starkov, Victor Tsetlin, Yuri Utkin
Format: | Article |
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Diterbitkan: | MDPI AG 2024-02-01 |
Deskripsi
Phospholipases A<sub>2</sub> (PLA<sub>2</sub>s) are a large family of snake toxins manifesting diverse biological effects, which are not always related to phospholipolytic activity. Snake venom PLA<sub>2</sub>s (svPLA<sub>2</sub>s) are extracellular proteins with a molecular mass of 13–14 kDa. They are present in venoms in the form of monomers, dimers, and larger oligomers. The cardiovascular system is one of the multiple svPLA<sub>2</sub> targets in prey organisms. The results obtained previously on the cardiovascular effects of monomeric svPLA<sub>2</sub>s were inconsistent, while the data on the dimeric svPLA<sub>2</sub> crotoxin from the rattlesnake <i>Crotalus durissus terrificus</i> showed that it significantly reduced the contractile force of guinea pig hearts. Here, we studied the effects of the heterodimeric svPLA<sub>2</sub> HDP-1 from the viper <i>Vipera nikolskii</i> on papillary muscle (PM) contractility and the tension of the aortic rings (ARs). HDP-1 is structurally different from crotoxin, and over a wide range of concentrations, it produced a long-term, stable, positive inotropic effect in PMs, which did not turn into contractures at the concentrations studied. This also distinguishes HDP-1 from the monomeric svPLA<sub>2</sub>s, which at high concentrations inhibited cardiac function. HDP-1, when acting on ARs preconstricted with 10 μM phenylephrine, induced a vasorelaxant effect, similar to some other svPLA<sub>2</sub>s. These are the first indications of the cardiac and vascular effects of true vipers’ heterodimeric svPLA<sub>2</sub>s.