Rapakinin, Arg-Ile-Tyr, derived from rapeseed napin, shows anti-opioid activity via the prostaglandin IP receptor followed by the cholecystokinin CCK(2) receptor in mice.
Rapakinin, Arg-Ile-Tyr, is a vasorelaxing, anti-hypertensive and anorexigenic peptide derived from rapeseed napin. In this study, we found that rapakinin intracerebroventricularly administered to mice inhibited the analgesic effect of morphine, evaluated by the tail-pinch test. The anti-opioid activity of rapakinin was blocked by LY225910, an antagonist of the cholecystokinin (CCK) CCK(2) receptor, but not by lorglumide, an antagonist of the CCK(1) receptor. The anti-opioid activity of rapakinin was also blocked by CAY10441, an antagonist of the prostaglandin (PG) IP receptor. These results suggest that the anti-opioid activity of rapakinin is mediated by the CCK(2) and IP receptors. The anti-opioid activity induced by ciprostene, an IP receptor agonist, was blocked by LY225910, while that of CCK-8 was not blocked by CAY10441. Thus, it is demonstrated that the CCK-CCK(2) system was activated downstream of the PGI(2)-IP receptor system. Taken together, rapakinin shows anti-opioid activity via the activation of the PGI(2)-IP receptor system followed by the CCK-CCK(2) receptor system.
Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan. yyamada@kais.kyoto-u.ac.jp
Yuko
Y
Yamada
Kousaku
K
Ohinata
Andrzej W
AW
Lipkowski
Masaaki
M
Yoshikawa
D055516:2S Albumins, Plant / Q000737:chemistry*; D000818:Animals; D019540:Area Under Curve; D029741:Brassica rapa / Q000737:chemistry; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010147:Pain Measurement; D052999:Quinazolinones / Q000008:administration & dosage / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012844:Sincalide / Q000494:pharmacology
C435663:2-(2-(5-bromo-1H-indol-3-yl)ethyl)-3-(1-methylethoxyphenyl)-4-(3H)-quinazolinone; D055516:2S Albumins, Plant; D009292:Narcotic Antagonists; D009842:Oligopeptides; C491910:Ptgir protein, mouse; D052999:Quinazolinones; D043887:Receptor, Cholecystokinin B; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; C514605:arginyl-isoleucyl-tyrosine; D009020:Morphine; C050363:napin protein, Brassica napus; D011464:Epoprostenol; C045329:ciprostene; D012844:Sincalide