An enzymatically stable kyotorphin analog induces pain in subattomol doses.
Intraplantar injection of the enzymatically stable, N-methylated kyotorphin analog Tyr(NMe)-Arg-OH produced marked and sharp nociceptive flexor responses in a dose-dependent manner. A significant response was observed with this compound at a dose of 0. 01 amol (6000 molecules). Tyr(NMe)-Arg-OH-nociception was completely blocked by the kyotorphin antagonist leucyl-arginine and its enzymatically stable, N-methylated analog, as well as by CP-99994, a specific neurokinin 1 antagonist. These findings suggest that the nociceptive effect produced by Tyr(NMe)-Arg-OH in subattomol doses occurs via specific interaction with the kyotorphin receptor and that the extraordinary potency observed may result from amplification through local substance P release.
Ueda
H
H
Department of Molecular Pharmacology and Neuroscience, Nagasaki University School of Pharmaceutical Sciences, 1-14 Bunkyo-machi, 852-8521, Nagasaki, Japan. ueda@net.nagasaki-u.ac.jp
Inoue
M
M
Weltrowska
G
G
Schiller
P W
PW
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D004723:Endorphins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D064729:Neurokinin-1 Receptor Antagonists; D010146:Pain / Q000139:chemically induced*
D000700:Analgesics; D004723:Endorphins; D064729:Neurokinin-1 Receptor Antagonists; C019448:kyotorphin