Role of kinins and sensory neurons in the rat pleural leukocyte migration induced by Phoneutria nigriventer spider venom.
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.
Costa
Soraia K P
SK
Department of Pharmacology, Faculty of Medical Sciences, UNICAMP, P.O. Box 6111, 13081-970, (SP), Campinas, Brazil.
Moreno
Ronilson A
RA
Esquisatto
Laura C M
LC
Juliano
Luiz
L
Brain
Susan D
SD
De Nucci
Gilberto
G
Antunes
Edson
E
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
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