Neurokinin 1 receptor activates transient receptor potential-like currents in noradrenergic A7 neurons in rats.
Noradrenergic (NAergic) A7 neurons are involved in modulating nociception by releasing noradrenaline in the dorsal spinal cord. Since NAergic A7 neurons receive dense Substance P (Sub-P) releasing terminals from ventromedial medulla, here we tested the effect of Sub-P on them. Bath application of Sub-P induced an inward current (I(Sub-P)) in NAergic neurons, which was significantly blocked by Neurokinin 1 (NK1) receptor antagonist. The I(Sub-P) was reversed at approximately -20 mV, blocked by several TRP channel blockers, enhanced by OAG and negatively regulated by PKC. Immunohistochemistry staining showed that NAergic A7 neurons express high level of TRPC6 channel proteins, which is consistent with pharmacological properties of I(Sub-P) shown above, as TRPC6 channel is shown to be augmented by OAG and inhibited by PKC. In conclusion, the above results provide mechanism underlying postsynaptic action of Sub-P on NAergic A7 neurons and a role for TRPC6 channel in NAergic pain modulation.
Min
Ming-Yuan
MY
Institute of Zoology, College of Life Science, National Taiwan University, Taipei 106, Taiwan; Department of Life Science, College of Life Science, National Taiwan University, Taipei 106, Taiwan.
Shih
Pei-Yu
PY
Wu
Yu-Wei
YW
Lu
Hsin-Wei
HW
Lee
Meng-Larn
ML
Yang
Hsiu-Wen
HW
D000818:Animals; D000831:Animals, Newborn; D000970:Antineoplastic Agents / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D054833:Isoindoles / Q000494:pharmacology; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D064729:Neurokinin-1 Receptor Antagonists; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology; D013373:Substance P / Q000494:pharmacology; D013498:Suramin / Q000494:pharmacology; D050052:TRPC Cation Channels / Q000378:metabolism*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D004963:Estrenes; D018691:Excitatory Amino Acid Antagonists; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D018377:Neurotransmitter Agents; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D018040:Receptors, Neurokinin-1; D050052:TRPC Cation Channels; C492145:Trpc6 protein, rat; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; D013498:Suramin; D004299:Dopamine beta-Hydroxylase; C013411:biocytin; D008239:Lysine; D009638:Norepinephrine