Lysophosphatidic acid-induced, pertussis toxin-sensitive nociception through a substance P release from peripheral nerve endings in mice.
The intraplantar injection of lysophosphatidic acid (LPA) at doses of 0.1-100 pmol into the hind limb of mice showed dose-dependent nociceptive flexor responses. Repeated challenges of LPA at 100 pmol every 5 min showed constant responses at least for 30 min. The prior application of pertussis toxin (PTX) at a dose of 10 ng markedly reduced the following LPA (100 pmol) actions. In addition, the intraplantar application of CP-99994 (1 pmol), a substance P (NK1) receptor antagonist, but not CP-100263 (1 pmol), an inactive derivative, also markedly reduced the LPA responses. These findings suggest that LPA has a nociception-producing activity on sensory neurons through G(i/o) activation and substance P release from nociceptor endings.
Renbäck
K
K
Department of Molecular Pharmacology and Neuroscience, Nagasaki University School of Pharmaceutical Sciences, Japan.
Inoue
M
M
Ueda
H
H
D000818:Animals; D006614:Hindlimb / Q000294:innervation; D008246:Lysophospholipids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009411:Nerve Endings / Q000187:drug effects / Q000502:physiology*; D064729:Neurokinin-1 Receptor Antagonists; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D010525:Peripheral Nerves / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D037342:Pertussis Toxin; D010880:Piperidines / Q000494:pharmacology; D013237:Stereoisomerism; D013373:Substance P / Q000378:metabolism*; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D008246:Lysophospholipids; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D010566:Virulence Factors, Bordetella; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D013373:Substance P; D037342:Pertussis Toxin