Abstract
The leukocyte migration induced by Phoneutria nigriventer spider venom (PNV) has been investigated in rats using the pleurisy model. Intrapleural injection of PNV (10-100 microg/cavity) caused a dose- and time-dependent leukocyte accumulation. The bradykinin B(2) receptor antagonist Hoe 140 (0.5 mg/kg) substantially inhibited PNV-induced cell accumulation, whereas the angiotensin-converting enzyme inhibitor captopril (2 mg/kg) potentiated by 80% this effect. The non-specific kallikrein inhibitor aprotinin and the plasma kallikrein inhibitor soybean trypsin inhibitor greatly reduced PNV-induced leukocyte migration, whereas the selective tissue kallikrein inhibitor P(ac)-F-S-R-EDDnp failed to affect PNV-induced responses. Treatment of rats with capsaicin (50 mg/kg) at the neonatal stage resulted in 67% inhibition of the PNV-induced cell migration. The neurokinin NK(1) receptor antagonist SR140333, but not the NK(2) receptor antagonist SR48968, reduced by 55% venom-induced cell accumulation. We conclude that bradykinin generation is involved in the PNV-induced pleural leukocyte migration in rats, where it can directly activate sensory nerves contributing to a neurogenic inflammatory mechanism.
MeSH terms
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Angiotensin-Converting Enzyme Inhibitors / pharmacology
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Animals
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Aprotinin / pharmacology
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Benzamides / pharmacology
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Bradykinin / metabolism*
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Bradykinin / pharmacology
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Bradykinin Receptor Antagonists
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Capsaicin / pharmacology
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Chemotaxis, Leukocyte / drug effects*
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Chemotaxis, Leukocyte / physiology
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Dose-Response Relationship, Drug
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Leukocytes / drug effects
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Leukocytes / immunology
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Leukocytes / metabolism
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Male
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Neurogenic Inflammation / chemically induced*
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Neurogenic Inflammation / metabolism
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Neurogenic Inflammation / physiopathology
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Neurokinin-1 Receptor Antagonists
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Neurons, Afferent / drug effects*
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Neurons, Afferent / metabolism
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Piperidines / pharmacology
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Pleura / drug effects
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Pleura / innervation*
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Pleura / physiopathology
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Pleurisy / chemically induced*
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Pleurisy / metabolism
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Pleurisy / physiopathology
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Quinuclidines / pharmacology
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Rats
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Rats, Wistar
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Receptors, Bradykinin / metabolism
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Receptors, Neurokinin-1 / metabolism
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Soybean Proteins / pharmacology
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Spider Venoms / toxicity*
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Trypsin Inhibitors / pharmacology
Substances
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Angiotensin-Converting Enzyme Inhibitors
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Benzamides
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Bradykinin Receptor Antagonists
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Neurokinin-1 Receptor Antagonists
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Piperidines
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Quinuclidines
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Receptors, Bradykinin
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Receptors, Neurokinin-1
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Soybean Proteins
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Spider Venoms
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Trypsin Inhibitors
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SR 140333
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SR 48968
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Aprotinin
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Capsaicin
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Bradykinin