Antagonistic effects of CompB on orphanin FQ-induced colonic contractions in rats.
Antagonistic effects of CompB on orphanin FQ-induced colonic contractions in rats.
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CompB 对孤啡肽 FQ 诱导的大鼠结肠收缩的拮抗作用。
DOI：
10.1016/s0014-2999(02)02474-3
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发表时间：
2002
影响因子：
5
通讯作者：
Takahashi,Toku
中科院分区：
文献类型：
--
作者：
Tada,Hitoshi;Nakagawa,Kazuhiko;Yamamura,Takehira;Takahashi,Toku
孤啡肽FQ已显示刺激大鼠结肠收缩而不影响上消化道运动。本实验研究了一种新的可能的FQ受体拮抗剂1-[（3R，4 R）-1-环辛基甲基-3-羟甲基-4-哌啶基]-3-乙基-1，3-二氢-2H-苯并咪唑-2-酮（CompB）在体内和体外是否对FQ诱导的大鼠结肠收缩有拮抗作用。孤啡肽FQ-（1-17）和孤啡肽FQ-（1-13）在体外以浓度依赖性方式（10−10-10− 6 M）引起远端结肠的环行肌收缩。CompB（10−7-10− 6 M）对FQ-（1-17）中的E2和FQ-（1-13）诱导的收缩中的E2引起显著抑制，而不影响自发收缩。孤啡肽FQ-（1-17）在体内也引起远端结肠的收缩。CompB（30-300 nmol/kg）可剂量依赖性地拮抗FQ-（1-17）（400 pmol/kg）引起的收缩作用。相反，CompB在体内和体外对强啡肽A诱导的收缩没有抑制作用。这表明CompB是一种选择性的大鼠结肠FQ受体拮抗剂。
Orphanin FQ has been shown to stimulate colonic contraction without affecting upper gastrointestinal motility in rats. We studied whether a new putative orphanin FQ receptor antagonist, 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1, 3-dihydro-2H-benzimidazol-2-one (CompB), has antagonistic effects on orphanin FQ-induced colonic contractions in vivo and in vitro in rats. Orphanin FQ-(1–17) and orphanin FQ-(1–13) caused contractions of the circular muscle of the distal colon in a concentration dependent manner (10−10–10−6M) in vitro. CompB (10−7–10−6M) caused a significant inhibition on orphanin FQ-(1–17) and orphanin FQ-(1–13)-induced contractions without affecting the spontaneous contractions. Orphanin FQ-(1–17) also caused contractions of the distal colon in vivo. ED50dose of orphanin FQ-(1–17) (400 pmol/kg)-induced contractions were significantly antagonized by CompB (30–300 nmol/kg) in a dose-dependent manner. In contrast, CompB had no inhibitory effects on dynorphin A-induced contractions in vivo and in vitro. These indicate that CompB is a selective orphanin FQ receptor antagonist of the rat colon.