Uterine region-dependent differences in responsiveness to prostaglandins in the non-pregnant porcine myometrium
Uterine region-dependent differences in responsiveness to prostaglandins in the non-pregnant porcine myometrium
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DOI：
10.1016/j.prostaglandins.2004.11.002
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发表时间：
2005-01-01
影响因子：
2.9
通讯作者：
Taneike, T
中科院分区：
文献类型：
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作者：
Cao, JS;Yosida, M;Taneike, T
为了阐明前列腺素受体的子宫区域依赖性分布，我们比较了选择性前列腺素受体激动剂(FP、EP3、DP、EP2)和自然产生的前列腺素(PGF(2α)、PGE(2)、PGD(2))对未孕猪子宫三个不同区域(角、体和宫颈)纵肌和环肌的机械反应。用RT-PCR和Western blotting检测FP受体和环氧合酶(COX-1和COX-2)在相应区域的表达水平。纵肌和环肌对FP激动剂氟前列烯醇和PGF(2α)的收缩反应在角部最强，在体部和宫颈较弱。FP？mRNA和蛋白的表达水平？受体在角部最高，与收缩反应一致。EP3激动剂ONO-AE-248引起两个肌层的收缩，但仅在纵肌观察到与区域相关的反应性差异。ONO-AE1-259(EP2激动剂)抑制子宫肌层的自发收缩，在宫颈的抑制作用明显更强。前列腺素E_2引起收缩(<；100 nM，角=宫颈)和抑制(>；300 nM，角=宫颈)，这取决于两个肌肉层中的浓度。DP激动剂BW245C抑制自发性收缩，在纵行肌(颈=体角)有明显的区域依赖性不同反应。在未孕猪子宫中检测到COX-1，但未检测到COX-2。COX-1在纵肌中的表达水平不同，在环行肌中的表达水平相同。SC-560抑制所有区域纵肌的自发收缩。本研究结果表明，收缩(FP和EP3，宫颈)和松弛(EP2和DP，宫颈和GT；角质)前列腺素受体和COX-1在猪子宫中存在区域性的异质性分布。结果还表明，内源性前列腺素参与了自发性子宫收缩的调节。环氧合酶-1和前列腺素受体的区域相关差异可能是产生子宫运动梯度所必需的，该梯度从子宫角到宫颈，负责管理子宫腔内容物的运动。(C)2004 Elsevier Inc.保留所有权利。
To clarify the uterine region-dependent distribution of prostanoid receptors, we compared the mechanical responses to selective prostanoid receptor agonists; (FP, EP3, DP, EP2) and naturally occurring prostaglandins (PGF(2 alpha), PGE(2), PGD(2)) in longitudinal and circular muscles isolated from three different regions (cornu, corpus and cervix) of the non-pregnant porcine uterus. Expression levels of FP receptor and cyclooxygenase (COX-1 and COX-2) in the respective regions were also examined using RT-PCR and Western blotting. The contractile responses to fluprostenol (an FP agonist) and PGF(2 alpha) in both longitudinal and circular muscles were strongest in the cornu but weak in the corpus and cervix. Expression levels of mRNA and protein of FP? receptor were highest in the cornu, consistent with the contractile responses. ONO-AE-248 (an EP3 agonist) caused contraction of both muscle layers, but region-related difference in responsiveness was observed only in the longitudinal muscle. ONO-AE1-259 (an EP2 agonist) inhibited spontaneous contraction of the myometrium, and inhibition was conspicuously stronger in the cervix. PGE2 caused contraction (< 100 nM, cornu > corpus = cervix) and inhibition (> 300 nM, cornu = corpus < cervix) of contractility depending on the concentration in both muscle layers. BW245C (a DP agonist) inhibited the spontaneous contraction, and region-dependent different responsiveness was marked in the longitudinal muscle (cervix = corpus > cornu). COX-1 but not COX-2 was detected in the non-pregnant porcine uterus. Expression level of COX-1 was different in the longitudinal muscle (cornu > corpus = cervix) but the same in the circular muscle. SC-560 inhibited the spontaneous contraction of longitudinal muscles in all regions. The results of the present study indicate that there are region-related heterogeneous distributions of contractile (FP and EP3, comu > cervix) and relaxant (EP2 and DP, cervix > cornu) prostanoid receptors and COX-1 in the porcine uterus. The results also suggest involvement of endogenous PGs in the regulation of spontaneous uterine contractility. Region-related differences in COX-1 and prostanoid receptors might be necessary to produce a gradient of uterine motility decreasing from the cornu to the cervix that manages movement of luminal contents. (c) 2004 Elsevier Inc. All rights reserved.