In vivo signal transduction of tetrodotoxin-sensitive nociceptive responses by substance P given into the planta of the mouse hind limb.
1. We developed a simple and sensitive peripheral analgesic test in mice. 2. Substance P (SP) given into the planta (i.pl.) of the mouse hind limb produced a flexor response. The flexor response was dependent on SP doses (0.1-100 pmol, i.pl.). When SP (10 pmol) was given every 5 min, there were stable flexor responses. These nociceptive responses were completely abolished by CP-96,345, a neurokinin 1 receptor antagonist. 3. SP-induced responses were also blocked by several signal transduction-related compounds, such as tetrodotoxin, EGTA, and U73122, a selective phospholipase C inhibitor. 4. These findings suggest that SP depolarizes peripheral nerve endings, possibly through inositol trisphosphate (Ins P3)-gated Ca2+ influx, followed by induction of action potentials in the peripheral axons of primary afferent neurons.
Department of Molecular Pharmacology and Neuroscience, Nagasaki University School of Pharmaceutical Sciences, Japan.
M
M
Inoue
S
S
Tokuyama
H
H
Nakayamada
H
H
Ueda
D000200:Action Potentials / Q000187:drug effects; D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D004533:Egtazic Acid / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D006614:Hindlimb / Q000294:innervation; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D017136:Ion Transport; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008959:Models, Neurological; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000187:drug effects* / Q000502:physiology; D012018:Reflex / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013373:Substance P / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D001713:Biphenyl Compounds; D004963:Estrenes; D009498:Neurotoxins; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D018040:Receptors, Neurokinin-1; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D013373:Substance P; D013779:Tetrodotoxin; D004533:Egtazic Acid; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D043265:Phosphatidylinositol Diacylglycerol-Lyase; C066892:CP 96345