title: Morphine has an antinociceptive effect through activation of the okadaic-acid-sensitive Ser/Thr protein phosphatases PP 2 A and PP5 estimated by tail-pinch test in mice.
abstract: Although the serine/threonine protein kinases involved in the pharmacological action of morphine are well recognized, the critical contribution of serine/threonine protein phosphatase (PP) has been appreciated on to a slight degree. We examined the involvement of subtypes of serine/threonine protein phosphatase (PP) in the antinociceptive effect of morphine in mice. The antinociceptive effect of subcutaneously administered morphine was attenuated by simultaneously intracerebroventricular (i.c.v.) or intrathecal (i.t.) injection of okadaic acid (OA), a PP inhibitor. To reveal which subtypes of PPs participated in the antinociceptive effect of morphine, mice received i.c.v. or i.t. injections of antisense oligodeoxynucleotide (AS-ODN) directed against either the PP 2 A or PP5 subtypes of PPs before assessment of morphine-induced antinociception. Pretreatment with AS-ODN against PP 2 A or PP5 via each route weakened the antinociceptive effect of morphine, accompanied by reduction of expression levels of PP in the periaqueductal gray (PAG) and the spinal cord. Subcutaneously administered morphine increased activity of OA-sensitive PPs in the PAG and the spinal cord in a dose-dependent manner; this was prevented by concurrent administration of naloxone. These results suggest that PP 2 A and PP5 are involved in the antinociceptive effect of morphine in mice.
authors.affiliation: Department of Pharmacology, Wakayama Medical University, Wakayama, 811-1 Kimiidera, Wakayama City, Wakayama 641-0012, Japan. tmaeda@wakayama-med.ac.jp
authors.forename: Takehiko
authors.initials: T
authors.lastname: Maeda
authors.forename: Wakako
authors.initials: W
authors.lastname: Hamabe
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Yohji
authors.initials: Y
authors.lastname: Fukazawa
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Kumamoto
authors.forename: Masanobu
authors.initials: M
authors.lastname: Ozaki
authors.forename: Shiroh
authors.initials: S
authors.lastname: Kishioka
mesh_terms: D000818:Animals; D019540:Area Under Curve; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage*; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage*; D009687:Nuclear Proteins / Q000378:metabolism*; D019319:Okadaic Acid / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012694:Serine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D009294:Narcotics; D009687:Nuclear Proteins; D019319:Okadaic Acid; D013912:Threonine; D009270:Naloxone; D012694:Serine; D009020:Morphine; D010749:Phosphoprotein Phosphatases; C089641:protein phosphatase 5