Intracellular ATP increases capsaicin-activated channel activity by interacting with nucleotide-binding domains.
Capsaicin (CAP)-activated ion channel plays a key role in generating nociceptive neural signals in sensory neurons. Here we present evidence that intracellular ATP upregulates the activity of capsaicin receptor channel. In inside-out membrane patches isolated from sensory neurons, application of CAP activated a nonselective cation channel (i(cap)). Further addition of ATP to the bath caused a significant increase in i(cap), with a K(1/2) of 3.3 mm. Nonhydrolyzable analogs of ATP, adenylimidodiphosphate and adenosine 5'-O-(3-thio)-triphosphate, also increased i(cap). Neither Mg(2+)-free medium nor inhibitors of various kinases blocked the increase in i(cap) induced by ATP. The enhancing effect of ATP was also observed in inside-out patches of oocytes expressing vanilloid receptor 1, a cloned capsaicin receptor. Single point mutations (D178N, K735R) within the putative Walker type nucleotide-binding domains abolished the effect of ATP. These results show that ATP increases i(cap) in sensory neurons by direct interaction with the CAP channel without involvement of phosphorylation.
Kwak
J
J
Sensory Research Group, Creative Research Initiatives, Seoul National University, College of Pharmacy, Kwanak, Shinlim San 56-1, Seoul 151-742, Korea.
Wang
M H
MH
Hwang
S W
SW
Kim
T Y
TY
Lee
S Y
SY
Oh
U
U
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D000266:Adenylyl Imidodiphosphate / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009711:Nucleotides / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D051381:Rats; D011955:Receptors, Drug / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D050916:TRPV Cation Channels; D015854:Up-Regulation / Q000187:drug effects; D014981:Xenopus
D004791:Enzyme Inhibitors; D009711:Nucleotides; D047428:Protein Kinase Inhibitors; D011955:Receptors, Drug; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D000266:Adenylyl Imidodiphosphate; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D012964:Sodium; D008274:Magnesium; D011188:Potassium; D002211:Capsaicin