Effects and mechanisms of supraspinal administration of rat/mouse hemokinin-1, a mammalian tachykinin peptide, on nociception in mice.
Rat/mouse hemokinin 1 (r/m HK-1) is a novel tachykinin peptide whose biological functions are not fully understood. This work was designed to observe the effects of r/m HK-1 in pain modulation at supraspinal level in mice using tail-flick test. Intracerebroventricular (i.c.v.) administration of r/m HK-1 (0.1, 0.3, 1, 3 nmol/mouse) dose-dependently induced potent analgesic effect (ED(50) = 0.2877 nmol/mouse). When r/m HK-1 co-injected (i.c.v.) with SR140333 (a selective NK(1) receptor antagonist), SR140333 could fully antagonize the analgesic effect of r/m HK-1. The maximal analgesic effect of r/m HK-1 (3 nmol/mouse) could also be reversed by naloxone (i.p., 2 mg/kg). However, i.c.v. low dose administration of r/m HK-1 (10, 3, 1 pmol/mouse) induced hyperalgesia with a "U" shape curve, which means that the maximal hyperalgesic effect appeared at 3 pmol/mouse, and this effect of r/m HK-1 could also be fully blocked by SR140333. Interestingly, [Nphe(1)]NC(1-13)NH(2), a selective opioid receptor like-1 (ORL-1) receptor antagonist, could fully reverse the maximal hyperalgesic effect of r/m HK-1 (3 pmol/mouse). In addition, when r/m HK-1 co-injected (i.c.v.) with SR48968 (a selective NK(2) receptor antagonist), SR48968 could hardly affect the nociceptive effects of r/m HK-1 either at nanomole concentration or at picomole concentration. These findings suggested that r/m HK-1 might play an important role in pain modulation at supraspinal level in mice and these effects were first elicited through the activation of NK(1) receptor, subsequently, whether activation of the classical opioid receptor or the ORL1 receptor depending on the dose of i.c.v. administration of r/m HK-1.
Fu
Cai-Yun
CY
Department of Biochemistry and Molecular Biology, School of Life Science, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
Kong
Zi-Qing
ZQ
Wang
Kai-Rong
KR
Yang
Qi
Q
Zhai
Kui
K
Chen
Qiang
Q
Wang
Rui
R
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001549:Benzamides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D058851:GPI-Linked Proteins; D006432:Hemochromatosis; D000071020:Hemochromatosis Protein; D007278:Injections, Spinal / Q000379:methods; D008297:Male; D008565:Membrane Proteins / Q000008:administration & dosage* / Q000627:therapeutic use; D051379:Mice; D008815:Mice, Inbred Strains; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000379:methods; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
D001549:Benzamides; D058851:GPI-Linked Proteins; C504414:HJV protein, mouse; D000071020:Hemochromatosis Protein; D008565:Membrane Proteins; D009292:Narcotic Antagonists; D010880:Piperidines; D011812:Quinuclidines; C113342:cyclo(N-benzylglycyl-phenylalanyl-tryptophyl-lysyl-threonyl-phenylalanyl); C085215:SR 140333; D009270:Naloxone; D013004:Somatostatin; C073839:SR 48968