Leukocyte recruitment to peritoneal cavity of rats following formalin injection: role of tachykinin receptors

J Pharmacol Sci. 2004 Apr;94(4):384-92. doi: 10.1254/jphs.94.384.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamides / pharmacology
  • Cell Movement / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Formaldehyde / administration & dosage*
  • Formaldehyde / pharmacology*
  • Injections, Intraperitoneal
  • Leukocytes / cytology
  • Leukocytes / drug effects
  • Leukocytes / physiology*
  • Models, Biological
  • Neurokinin A / metabolism
  • Neurokinin B / metabolism
  • Neurokinin-1 Receptor Antagonists
  • Peritoneal Cavity / physiology*
  • Peritoneal Lavage
  • Piperidines / pharmacology
  • Quinuclidines / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Neurokinin-1 / drug effects
  • Receptors, Neurokinin-2 / antagonists & inhibitors
  • Receptors, Neurokinin-2 / drug effects
  • Receptors, Neurokinin-3 / antagonists & inhibitors
  • Receptors, Neurokinin-3 / drug effects
  • Receptors, Tachykinin / antagonists & inhibitors*
  • Receptors, Tachykinin / drug effects
  • Substance P / metabolism
  • Time Factors

Substances

  • Benzamides
  • Neurokinin-1 Receptor Antagonists
  • Piperidines
  • Quinuclidines
  • Receptors, Neurokinin-1
  • Receptors, Neurokinin-2
  • Receptors, Neurokinin-3
  • Receptors, Tachykinin
  • SR 140333
  • Formaldehyde
  • Substance P
  • SR 48968
  • Neurokinin A
  • Neurokinin B
  • SR 142801