Narita Minoru, Ohnishi Orie, Narita Michiko, Aoki Takeshi, Suzuki Masami, Yajima Yoshinori, Funahashi Hisayuki, Shioda Seiji, Suzuki Tsutomu
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Brain Res. 2003 Apr 25;970(1-2):140-8. doi: 10.1016/s0006-8993(03)02301-1.
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.
本研究的目的是调查体内吗啡治疗是否能参与小鼠中脑导水管周围灰质（PAG）中磷脂酶Cγ1（PLCγ1）亚型的激活，这可能伴随着吗啡诱导的抗伤害感受反应。除了μ-阿片受体样免疫反应性（MOR-IR）外，在小鼠PAG切片中还观察到中等程度的PLCγ1样免疫反应性（PLCγ1-IR）。皮下注射吗啡后，在阳性细胞的细胞表面检测到强烈的PLCγ1-IR。皮下注射吗啡使PAG中表达磷酸化PLCγ1（p-PLCγ1）的细胞数量显著增加。通过脑室内预先用针对PLCγ1的反义寡脱氧核苷酸预处理来缺失PLCγ1基因，结果显示选择性μ-阿片受体激动剂[D-Ala(2)，N-Me-Phe(4)，Gly(5)-ol]脑啡肽（DAMGO）诱导的脊髓上抗伤害感受受到显著抑制。此外，脑室内预先用针对PLCγ1的特异性抗体处理，导致脑室内注射吗啡或DAMGO所产生的抗伤害感受呈浓度依赖性减弱。这些发现表明，体内吗啡治疗可激活小鼠PAG中的PLCγ1亚型，这至少部分与小鼠中μ-阿片受体激动剂诱导的脊髓上抗伤害感受的表达有关。
