title: Methoctramine analogues inhibit responses to capsaicin and protons in rat dorsal root ganglion neurons.
abstract: We have investigated the possibility that vanilloid receptors have a binding site for polyamines and determined the consequences of binding to such a site. Whole-cell and single-channel patch-clamp recordings were used to investigate the effect of the tetraamine, methoctramine, and 16 of its analogues on capsaicin and proton induced responses of foetal rat dorsal root ganglion neurons. All but two methoctramine analogues inhibited responses to 10 microM capsaicin with IC50 values in the range of 2-70 microM at a holding potential of -100 mV. Inhibition was generally non-competitive and voltage-dependent. Methoctramine at 10 microM reduced the single channel mean open time (>3-fold), but also increased the mean closed time (1.7-fold). Sustained responses to pH 5.4 were antagonized by methoctramine with similar potency to capsaicin responses. Similar data were obtained with adult rat dorsal root ganglion neurons. These data indicate that methoctramine analogues bind to vanilloid receptors to inhibit their function.
authors.affiliation: School of Biology, University of Nottingham, University Park, Nottingham, NG7 2RD, UK. ian.mellor@nottingham.ac.uk
authors.forename: Ian R
authors.initials: IR
authors.lastname: Mellor
authors.forename: Jane
authors.initials: J
authors.lastname: Ogilvie
authors.forename: Florentina
authors.initials: F
authors.lastname: Pluteanu
authors.forename: Richard H
authors.initials: RH
authors.lastname: Clothier
authors.forename: Terence L
authors.initials: TL
authors.lastname: Parker
authors.forename: Michela
authors.initials: M
authors.lastname: Rosini
authors.forename: Anna
authors.initials: A
authors.lastname: Minarini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Tumiatti
authors.forename: Carlo
authors.initials: C
authors.lastname: Melchiorre
mesh_terms: D000367:Age Factors; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D003959:Diamines / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D003959:Diamines; C054938:methoctramine; D002211:Capsaicin