Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Am J Physiol Gastrointest Liver Physiol. 2009 Nov;297(5):G886-93. doi: 10.1152/ajpgi.00184.2009.
Progesterone (P4) inhibits the gastrointestinal muscle contraction by downregulating Galpha(q/11) proteins that mediate contraction, by upregulating Galpha(s) proteins that mediate relaxation, and by altering the pattern of cyclooxygenase (COX) enzymes and prostaglandins. We aimed to examine whether P4 treatment of guinea pigs in vivo affects basal colon motility [basal motility index (MI)] by altering the levels and actions of PGF(2alpha) and PGE(2). Guinea pigs were treated with intramuscular (IM) P4 for 4 days. The BASAL MI, the PGF(2alpha)-induced contraction, and PGE(2)-induced inhibition of contraction were examined in muscle strips and cells. The levels of PGF(2alpha) and PGE(2) were measured by radioimmunoassay. Treatment with P4 reduced the basal MI, the levels of PGF(2alpha), and PGF(2alpha)-induced contraction. P4 increased PGE(2) levels, and PGE(2) induced relaxation. Pretreatment with IM RU-486 (10 mg/kg per day), a P4 receptor antagonist, 1 h before P4 blocked the actions of P4. The PGF(2alpha) antagonist Al-1180 abolished basal MI and PGF(2alpha)-induced contraction. N-ethylmaleimide, which blocks unoccupied membrane receptors, blocked Ach and VIP actions but had no effect on PGF(2alpha) and PGE(2) effects. A COX-1 inhibitor decreased and a COX-2 inhibitor increased PGF(2alpha) levels; GTPgammaS increased and GDPbetaS decreased the levels of PGF(2alpha). Galpha(q/11) protein antibodies (Abs) reduced PGF(2alpha) levels, and Galpha(i3) Abs blocked its motor actions. Galphas Abs increased PGF(2alpha) but decreased PGE(2) levels. We concluded that P4 decreases basal MI by reducing PGF(2alpha) levels caused by downregulation of Galpha(q/11) and that PGF(2alpha)-induced contraction was blocked by downregulating Galpha(i3). P4 also decreased the basal MI by increasing PGE(2) levels, and PGE(2) induced relaxation by upregulating Galpha(s) proteins.
孕激素（P4）通过下调介导收缩的Gαq/11 蛋白、上调介导松弛的 Gαs 蛋白以及改变环氧化酶（COX）酶和前列腺素的模式来抑制胃肠道肌肉收缩。我们旨在研究体内 P4 处理豚鼠是否通过改变 PGF（2α）和 PGE（2）的水平和作用来影响基础结肠运动[基础运动指数（MI）]。豚鼠接受肌肉内（IM）P4 治疗 4 天。在肌肉条和细胞中检查 PGF（2α）诱导的收缩和 PGE（2）诱导的收缩抑制的 BASAL MI。通过放射免疫测定法测量 PGF（2α）和 PGE（2）的水平。P4 处理降低了基础 MI、PGF（2α）水平和 PGF（2α）诱导的收缩。P4 增加了 PGE（2）水平，PGE（2）诱导了松弛。在 P4 前 1 小时预先用肌肉内 RU-486（10mg/kg/天），一种 P4 受体拮抗剂预处理，可阻断 P4 的作用。PGF（2α）拮抗剂 Al-1180 消除了基础 MI 和 PGF（2α）诱导的收缩。阻断未占据的膜受体的 N-乙基马来酰亚胺阻断了 Ach 和 VIP 的作用，但对 PGF（2α）和 PGE（2）的作用没有影响。COX-1 抑制剂降低，COX-2 抑制剂增加 PGF（2α）水平；GTPγS 增加，GDPβS 降低 PGF（2α）水平。Gαq/11 蛋白抗体（Abs）降低了 PGF（2α）水平，Gαi3Abs 阻断了其运动作用。Galphas Abs 增加了 PGF（2α）但降低了 PGE（2）水平。我们的结论是，P4 通过下调 Galpha（q/11）降低 PGF（2α）水平来降低基础 MI，PGF（2α）诱导的收缩被下调 Galpha（i3）阻断。P4 还通过增加 PGE（2）水平降低基础 MI，通过上调 Galpha（s）蛋白诱导松弛。
