title: Differential expression of phosphorylated Ca2+/calmodulin-dependent protein kinase II and phosphorylated extracellular signal-regulated protein in the mouse hippocampus induced by various nociceptive stimuli.
abstract: In the present study, we characterized differential expressions of phosphorylated Ca(2+)/calmodulin-dependent protein kinase IIalpha (pCaMKIIalpha) and phosphorylated extracellular signal-regulated protein (pERK) in the mouse hippocampus induced by various nociceptive stimuli. In an immunoblot study, s.c. injection of formalin and intrathecal (i.t.) injections of glutamate, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1 beta) significantly increased pCaMKIIalpha expression in the hippocampus, but i.p. injections of acetic acid did not. pERK1/2 expression was also increased by i.t. injection of glutamate, TNF-alpha, and IL-1beta but not by s.c. injections of formalin or i.p. injections of acetic acid. In an immunohistochemical study, we found that increased pCaMKIIalpha and pERK expressions were mainly located at CA3 or the dentate gyrus of the hippocampus. In a behavioral study, we assessed the effects of PD98059 (a MEK 1/2 inhibitor) and KN-93 (a CaMKII inhibitor) following i.c.v. administration on the nociceptive behaviors induced by i.t. injections of glutamate, pro-inflammatory cytokines (TNF-alpha or IL-1beta), and i.p. injections of acetic acid. PD98059 as well as KN-93 significantly attenuated the nociceptive behavior induced by glutamate, pro-inflammatory cytokines, and acetic acid. Our results suggest that (1) pERKalpha and pCaMK-II located in the hippocampus are important regulators during the nociceptive processes induced by s.c. formalin, i.t. glutamate, i.t. pro-inflammatory cytokines, and i.p. acetic acid injection, respectively, and (2) the alteration of pERK and pCaMKIIalpha in nociceptive processing induced by formalin, glutamate, pro-inflammatory cytokines and acetic acid was modulated in a different manner.
authors.affiliation: Division of Recombinant Product, Biopharmaceutical Bureau, Korea Food and Drug Administration, 194 Tongilro, Eunpyeong-gu, Seoul, 122-704, Republic of Korea.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Seo
authors.forename: M-S
authors.initials: MS
authors.lastname: Kwon
authors.forename: H-W
authors.initials: HW
authors.lastname: Choi
authors.forename: S-M
authors.initials: SM
authors.lastname: Choi
authors.forename: Y-W
authors.initials: YW
authors.lastname: Kim
authors.forename: J-K
authors.initials: JK
authors.lastname: Lee
authors.forename: S-H
authors.initials: SH
authors.lastname: Park
authors.forename: J-S
authors.initials: JS
authors.lastname: Jung
authors.forename: H-W
authors.initials: HW
authors.lastname: Suh
mesh_terms: D019342:Acetic Acid; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001596:Benzylamines / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D005557:Formaldehyde; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D053583:Interleukin-1beta; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010146:Pain / Q000139:chemically induced / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha; D000096926:Benzenesulfonamides
chemical_list: D019342:Acetic Acid; D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D048049:Extracellular Signal-Regulated MAP Kinases; D005419:Flavonoids; D005557:Formaldehyde; D018698:Glutamic Acid; D053583:Interleukin-1beta; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C072105:KN 93; D000096926:Benzenesulfonamides; C517671:Camk2a protein, mouse; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one