Serotonin-dependent collagenase induction in rat myometrial smooth muscle cells: mediation by the 5-HT2 receptor.
Serotonin-dependent collagenase induction in rat myometrial smooth muscle cells: mediation by the 5-HT2 receptor.
复制标题
大鼠子宫平滑肌细胞中血清素依赖性胶原酶诱导：5-HT2 受体的介导。
DOI：
10.1016/0303-7207(93)90256-j
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发表时间：
1993
影响因子：
4.1
通讯作者：
Jeffrey,JJ
中科院分区：
文献类型：
--
作者：
Rydelek-Fitzgerald,L;Wilcox,BD;Teitler,M;Jeffrey,JJ
最近的研究表明，血清素（5-羟色胺; 5-HT）是诱导培养的大鼠和人子宫肌层平滑肌细胞间质胶原酶所必需的。本研究旨在确定哪种5-羟色胺受体亚型介导这些细胞中胶原酶的诱导。[125 DOI（±）-1-（2，5-二甲氧基-4-[125 I]碘苯基）-2-氨基丙烷）是一种5-HT 2受体激动剂，与子宫肌层细胞膜上的位点特异性结合，其结合特征与脑5-HT 2受体的结合特征基本相同。对其他5-羟色胺受体亚型（5-HT 1和5-HT 3）具有选择性的放射性配体未能产生可检测的结合。北方印迹分析表明子宫平滑肌细胞培养物中存在5-HT 2 mRNA，而未检测到5-HT 1A和5-HT 1c受体的转录本。此外，RT-PCR表明新鲜分离的子宫组织中也存在5-HT 2受体mRNA。5-HT 2受体的选择性拮抗剂酮色林和螺哌隆对子宫肌层培养物中的降钙素介导的胶原酶诱导表现出浓度依赖性抑制。这些拮抗剂产生的IC 50值分别为4.7 nM和2.7 nM，这是5-HT 2受体介导的反应所预期的值的特征。此外，一些选择性5-HT 2受体激动剂（quipazine，α-methyl-serotonin，DOI）模拟了5-羟色胺诱导胶原酶产生的能力，而对5-HT 1和5-HT 3受体亚型选择性的化合物几乎没有影响。这些结果表明，5-羟色胺诱导子宫平滑肌细胞胶原酶的能力是由5-HT 2受体亚型介导的，该受体可能是该外周细胞中唯一的5-羟色胺受体亚型。
Recent studies have shown that serotonin (5-hydroxytryptamine; 5-HT) is required for the induction of interstitial collagenase in cultured rat and human myometrial smooth muscle cells. The present study was performed to determine which serotonin receptor subtype mediates the induction of collagenase in these cells.[125 I] DOI (±)-l-(2, 5-dimethoxy-4-[125 I] iodophenyl)-2-aminopropane), a 5-HT 2 receptor agonist radioligand, bound specifically to sites in myometrial cell membranes, and exhibited binding characteristics essentially identical to those observed with brain 5-HT 2 receptors. Radioligands selective for other serotonin receptor subtypes (5-HT 1 and 5-HT 3) failed to yield detectable binding. Northern blot analysis demonstrated the presence of 5-HT 2 mRNA in the uterine smooth muscle cell cultures, whereas transcripts for 5-HT 1A and 5-HT 1c receptors were not detectable. Moreover, RT-PCR indicated that 5-HT 2 receptor mRNA is present in freshly isolated uterine tissue as well. Selective antagonists of the 5-HT 2 receptor, ketanserin and spiperone, displayed concentration-dependent inhibition of serotonin-mediated collagenase induction in the myometrial cultures. These antagonists yielded IC 50 values of 4.7 nM and 2.7 nM respectively, characteristic of values expected from a 5-HT 2 receptor-mediated response. In addition, a number of selective 5-HT 2 receptor agonists (quipazine, α-methyl-serotonin, DOI) mimicked the ability of serotonin to induce collagenase production, whereas compounds selective for 5-HT 1 and 5-HT 3 receptor subtypes had little effect. These results indicate that the ability of serotonin to induce collagenase in the uterine smooth muscle cells is mediated by the 5-HT 2 receptor subtype, and that this receptor may be the only serotonin receptor subtype in this peripheral cell.