Rho-kinase inhibitor, Y-27632, has an antinociceptive effect in mice.
The possible antinociceptive effect of a Rho-kinase inhibitor, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632), was investigated in mice by using the hot-plate and abdominal constriction response (writhing) tests. In addition, the expression of Rho-kinase protein (ROCK-2) was studied in the mouse brain and spinal cord by Western blotting. Male balb/c mice (n=8, for each group) were used in the experiment. Hot-plate latency and the number of writhes were recorded in control and in Y-27632-treated (1-5 mg/kg, i.p.) groups. Y-27632 (1 mg/kg) did not affect hot-plate latency; however, it considerably diminished the number of writhes, from 89+/-12 in control to 30+/-6 in the mice treated with 1 mg/kg Y-27632 (P=0.001). At a higher dose (5 mg/kg), Y-27632 prolonged the hot-plate latency from 8.7+/-1.0 s to 14.4+/-1.7 s (P=0.005) and decreased the number of writhes from 80+/-8 to 24+/-7 (P=0.002). Western blot analysis revealed that mouse spinal cord and brain homogenates expressed ROCK-2 protein. These results indicate that Rho-kinase may be involved in nociception and that its inhibitors, such as Y-27632, may represent a new type of antinociceptive drug.
Büyükafşar
Kansu
K
Department of Pharmacology, Medical Faculty, Mersin University, Campus Yenişehir 33169, Mersin, Turkey. kbuyukafsar@mersin.edu.tr
Yalçin
Ipek
I
Kurt
A Hakan
AH
Tiftik
R Nalan
RN
Sahan-Firat
Seyhan
S
Aksu
Fazilet
F
D000577:Amides / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010146:Pain / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D010147:Pain Measurement / Q000379:methods; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology; D054460:rho-Associated Kinases
D000577:Amides; D000700:Analgesics; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases