CRLI induces vascular smooth muscle relaxation and suggests a dual mechanism of eNOS activation by legume lectins via muscarinic receptors and shear stress
Copyright policy )CRLI induces vascular smooth muscle relaxation and suggests a dual mechanism of eNOS activation by legume lectins via muscarinic receptors and shear stress
Lectins are proteins able to recognize carbohydrates, without modifying their structure, via the carbohydrate-recognition domain (CRD). Here, the three-dimensional structure of the mannose-binding lectin isolated from Cymbosema roseum (CRLI) was determined with X-man molecule modeled into the carbohydrate recognition domain. CRLI relaxant activity in thoracic rat aorta was also investigated, and based on the results, a molecular docking of CRLI with heparan sulfate was performed to investigate the possible interaction with mechanoreceptors involved in vasorelaxation. CRLI (IC₅₀=12.4 μg mL(-)(1)) elicited vasorelaxant response (96%) in endothelialized rat aorta contracted with phenylephrine. Endothelium-derived relaxant factors, extracellular calcium (Ca(2+)e) and muscarinic receptors were also evaluated as putative participants in the CRLI relaxant effect. CRLI relaxant effect was blocked by L-NAME, a nonselective inhibitor of nitric oxide synthase (NOS), and partially inhibited in a calcium-free solution (0Ca) and by atropine, but it remained unchanged in the presence of indomethacin and TEA. In summary, our data suggest interaction between CRLI and muscarinic receptors located in vascular endothelial cells leading to NOS activation triggered by a mechanism that involves Ca(2+)e along with the ability of CRLI to interact with heparan sulfate, a highly rated mechanoreceptor involved in eNOS activation.
- Universidade Federal do Ceará Brazil
- State University of Ceará Brazil
- National Institute of Amazonian Research Brazil
- Universidade Regional do Cariri Brazil
- Universidade do Vale do Paraíba Brazil
Atropine, Male, Muscle Relaxation, Indomethacin, Vasodilatation, Muscle, Smooth, Vascular, Mechanoreceptor, Phenylephrine, Synchrotron Radiation, Stereochemistry, Enzyme Inhibitor, Enzyme Inhibitors, Aorta, Plant Proteins, Nos3 Protein, Muscarinic Receptor, Mannose-binding Lectin, Mannoside, X-ray Diffraction, Anti-Inflammatory Agents, Non-Steroidal, Fabaceae, Receptors, Muscarinic, Legume, Molecular Docking, Heparan Sulfate, NG-Nitroarginine Methyl Ester, Crystal Structure, Muscle, Smooth, Animals Experiment, Ng-nitroarginine Methyl Ester, Nitric Oxide Synthase Type III, Nitric Oxide, Electron, Protein Quaternary Structure, Mannose-Binding Lectin, Vascular, Endothelial Nitric Oxide Synthase, Animals Tissue, Animals, Humans, Controlled Study, Rats, Wistar, Shear Stress, Indometacin, Extracellular Calcium, Smooth Muscle Contractility, Manganese, Nonsteroid Antiinflammatory Agent, Vegetable Protein, Nonhuman, Rats, Molecular Weight, Enzyme Activation, Calcium Ion, Rat, Calcium, Sodium Ion, Metal Binding
Atropine, Male, Muscle Relaxation, Indomethacin, Vasodilatation, Muscle, Smooth, Vascular, Mechanoreceptor, Phenylephrine, Synchrotron Radiation, Stereochemistry, Enzyme Inhibitor, Enzyme Inhibitors, Aorta, Plant Proteins, Nos3 Protein, Muscarinic Receptor, Mannose-binding Lectin, Mannoside, X-ray Diffraction, Anti-Inflammatory Agents, Non-Steroidal, Fabaceae, Receptors, Muscarinic, Legume, Molecular Docking, Heparan Sulfate, NG-Nitroarginine Methyl Ester, Crystal Structure, Muscle, Smooth, Animals Experiment, Ng-nitroarginine Methyl Ester, Nitric Oxide Synthase Type III, Nitric Oxide, Electron, Protein Quaternary Structure, Mannose-Binding Lectin, Vascular, Endothelial Nitric Oxide Synthase, Animals Tissue, Animals, Humans, Controlled Study, Rats, Wistar, Shear Stress, Indometacin, Extracellular Calcium, Smooth Muscle Contractility, Manganese, Nonsteroid Antiinflammatory Agent, Vegetable Protein, Nonhuman, Rats, Molecular Weight, Enzyme Activation, Calcium Ion, Rat, Calcium, Sodium Ion, Metal Binding
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