Structure-activity relationship studies of spinorphin as a potent and selective human P2X(3) receptor antagonist.
Spinorphin, an endogenous antinociceptive peptide (LVVYPWT), showed potent and non-competitive antagonism at the ATP-activated human P2X3 receptor (IC50 = 8.3 pM) in a two-electrode voltage clamp assay with recombinant human P2X3 receptors expressed in Xenopus oocytes. Single alanine substitutions from 1st to 4th amino acids and the cyclic form of LVVYPWT sustained antagonistic properties at the human P2X3 receptors, whereas the threonine to alanine substitution resulted in an enhancing effect of the agonistic activity.
Jung
Kwan-Young
KY
Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
Moon
Hyoun Duk
HD
Lee
Ga Eun
GE
Lim
Hyun-Ho
HH
Park
Chul-Seung
CS
Kim
Yong-Chul
YC
D000818:Animals; D005260:Female; D006801:Humans; D051379:Mice; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D058919:Purinergic P2 Receptor Antagonists; D058469:Receptors, Purinergic P2X; D058477:Receptors, Purinergic P2X3; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D014981:Xenopus
D009842:Oligopeptides; C546407:P2RX3 protein, human; C546409:P2rx3 protein, mouse; D058919:Purinergic P2 Receptor Antagonists; D058469:Receptors, Purinergic P2X; D058477:Receptors, Purinergic P2X3; D011994:Recombinant Proteins; C082392:spinorphin