title: Role of kinins and sensory neurons in the rat pleural leukocyte migration induced by Phoneutria nigriventer spider venom.
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.
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, UNICAMP, P.O. Box 6111, 13081-970, (SP), Campinas, Brazil.
authors.forename: Soraia K P
authors.initials: SK
authors.lastname: Costa
authors.forename: Ronilson A
authors.initials: RA
authors.lastname: Moreno
authors.forename: Laura C M
authors.initials: LC
authors.lastname: Esquisatto
authors.forename: Luiz
authors.initials: L
authors.lastname: Juliano
authors.forename: Susan D
authors.initials: SD
authors.lastname: Brain
authors.forename: Gilberto
authors.initials: G
authors.lastname: De Nucci
authors.forename: Edson
authors.initials: E
authors.lastname: Antunes
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001920:Bradykinin / Q000378:metabolism* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002211:Capsaicin / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D020078:Neurogenic Inflammation / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D064729:Neurokinin-1 Receptor Antagonists; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D010994:Pleura / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology; D010998:Pleurisy / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018002:Receptors, Bradykinin / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D030262:Soybean Proteins / Q000494:pharmacology; D013111:Spider Venoms / Q000633:toxicity*; D014361:Trypsin Inhibitors / Q000494:pharmacology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001549:Benzamides; D065168:Bradykinin Receptor Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; D018002:Receptors, Bradykinin; D018040:Receptors, Neurokinin-1; D030262:Soybean Proteins; D013111:Spider Venoms; D014361:Trypsin Inhibitors; C085215:SR 140333; C073839:SR 48968; D007611:Aprotinin; D002211:Capsaicin; D001920:Bradykinin