Leukocyte recruitment to peritoneal cavity of rats following formalin injection: role of tachykinin receptors.
The aim of this work was to verify whether formalin would induce leukocyte recruitment following intraperitoneal (i.p.) injection in rats. Formalin (1.25 - 2.5%) induced cell recruitment, which was concentration- and time-dependent (0 - 24 h). Two peaks of leukocyte recruitment were observed. The first peak (from 2 to 4 h) was characterized by a mixed polymorphonuclear and lymphocyte cell population (representing an increase of 100 - 220% and 55 - 60%, respectively), whereas the second peak was characterized by a marked increase in lymphocytes at 24 h (representing an increase of 230%). Pretreatment of animals with specific antagonists for neurokinin NK(1), NK(2), and NK(3) receptors (SR140333, SR48968, and SR142801 compounds, respectively) reduced the early leukocyte increase (representing a significant reduction of 65%, 51%, and 46%, respectively), whereas only the treatment with NK(2)-specific antagonist reduced the late cell increase induced by formalin injection (amounting to a significant reduction of 48%). These results suggested that substance P, neurokinin A, and neurokinin B release accounted for formalin-induced cell migratory activity. The anti-inflammatory drug dexamethasone also reduced cell recruitment, which was mainly related to a reduction in 79% of the neutrophils at 4 h following 1.25% formalin injection, suggesting also a release of lipid mediators (eicosanoids and/or platelet-activating factor) and/or cytokines/chemokines by the formalin injection.
Santos
Júlia M M
JM
Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Brazil.
Tatsuo
Maria Aparecida K F
MA
Turchetti-Maia
Regina Maria M
RM
Lisboa
Marcela C G
MC
de Francischi
Janetti N
JN
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005557:Formaldehyde / Q000008:administration & dosage* / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008954:Models, Biological; D015288:Neurokinin A / Q000378:metabolism; D015287:Neurokinin B / Q000378:metabolism; D064729:Neurokinin-1 Receptor Antagonists; D010529:Peritoneal Cavity / Q000502:physiology*; D010533:Peritoneal Lavage; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D018040:Receptors, Neurokinin-1 / Q000187:drug effects; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000187:drug effects; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors / Q000187:drug effects; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors* / Q000187:drug effects; D013373:Substance P / Q000378:metabolism; D013997:Time Factors
D001549:Benzamides; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D018039:Receptors, Tachykinin; C085215:SR 140333; D005557:Formaldehyde; D013373:Substance P; C073839:SR 48968; D015288:Neurokinin A; D015287:Neurokinin B; C091554:SR 142801