title: Direct evidence for the activation of phospholipase C gamma 1 by in vivo treatment with morphine in the mouse periaqueductal gray matter.
abstract: The aim of the present study was to investigate whether in vivo morphine treatment could participate in the activation of phospholipase Cgamma1 (PLCgamma1) isoform in the mouse periaqueductal gray matter (PAG) which can be accompanied by antinociceptive responses induced by morphine. As well as mu-opioid receptor-like immunoreactivity (MOR-IR), moderate PLCgamma1-like immunoreactivity (PLCgamma1-IR) was noted in the mouse PAG section. After s.c. treatment with morphine, the intensive PLCgamma1-IR was detected in the cell surface of the positive cells. Treatment s.c. with morphine produced a robust increase in the number of phosphorylated-PLCgamma1 (p-PLCgamma1) expressing cells in the PAG. Deletion of PLCgamma1 gene by i.c.v. pretreatment with antisense oligodeoxynucleotide against PLCgamma1 revealed a significant inhibition of supraspinal antinociception induced by a selective mu-opioid receptor agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]enkephalin (DAMGO). Furthermore, i.c.v. pretreatment with a specific antibody to PLCgamma1 caused a concentration-dependent attenuation of antinociception produced by i.c.v. treatment with either morphine or DAMGO. These findings suggest that in vivo morphine treatment can activate PLCgamma1 isoform in the mouse PAG which can be, at least in part, associated with the expression of supraspinal antinociception induced by mu-opioid receptor agonists in the mouse.
authors.affiliation: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Narita
authors.forename: Orie
authors.initials: O
authors.lastname: Ohnishi
authors.forename: Michiko
authors.initials: M
authors.lastname: Narita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Aoki
authors.forename: Masami
authors.initials: M
authors.lastname: Suzuki
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Yajima
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Funahashi
authors.forename: Seiji
authors.initials: S
authors.lastname: Shioda
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D010487:Periaqueductal Gray / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D051966:Phospholipase C gamma; D010738:Type C Phospholipases / Q000032:analysis / Q000378:metabolism*
chemical_list: D009020:Morphine; D010738:Type C Phospholipases; D051966:Phospholipase C gamma