Functional prostaglandin E (EP) receptors in human penile corpus cavernosum.
Functional prostaglandin E (EP) receptors in human penile corpus cavernosum.
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人阴茎海绵体中的功能性前列腺素 E (EP) 受体。
DOI：
10.1038/sj.ijir.3901042
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Traish,A
中科院分区：
文献类型：
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作者：
Moreland,RB;Kim,N;Nehra,A;Goldstein,I;Traish,A
在这项研究中，我们研究了人海绵体组织和肝细胞平滑肌细胞中的功能性EP受体。用核糖核酸酶保护法检测EP2、EP3 I和EP3 II受体基因的表达。在肝细胞癌组织条的器官浴制备中，PGE1在浓度低于300 nM时引起剂量依赖的松弛。当浓度大于300 nM时，PGE1引起收缩。加入EP1/EP2/EP3受体拮抗剂AH6809可抑制这种收缩，并通过浓度大于1μM的PGE1促进进一步的松弛。EP1/EP3受体选择性激动剂17-苯基-前列腺素E2引起的收缩呈剂量依赖性，该作用可被EP1选择性拮抗剂SC51322部分减弱。在培养的肝癌SMC中，PGE1以剂量依赖的方式刺激cAMP的积累。有趣的是，AH6809显著抑制PGE1诱导的cAMP积聚。舒普司酮是一种选择性EP3受体激动剂，可诱导肝癌组织条的微弱收缩，但增强Forsklin诱导的肝癌SMC cAMP的合成。本研究结果提示，肝细胞癌和培养的血管平滑肌细胞表达EP1、EP2和EP3受体。这些受体通过不同的生化途径调节它们的反应，预计在调节平滑肌张力方面有不同的反应。因此，我们认为勃起组织对不同前列腺素的最终反应是单个EP受体亚型对给定配体的反应的整合。
In this study, we have characterized functional EP receptors in human corpus cavernosum (HCC) tissue and in HCC smooth muscle cells (SMC). Using RNase protection assays, we determined expression of EP2, EP3 I and EP3 II receptor mRNA. In organ bath preparations of HCC tissue strips, PGE 1 caused dose-dependent relaxation at concentrations below 300 nM. At concentrations greater than 300 nM, PGE 1 caused contraction. Addition of the EP1/EP2/EP3 receptor antagonist AH6809 inhibited this contraction and facilitated further relaxation through concentrations above 1 μM of PGE 1. The EP1/EP3 receptor selective agonist 17-phenyltrinor-PGE 2 caused dose-dependent contraction that was partially attenuated by SC51322, an EP1 selective antagonist. In cultures of HCC SMC, PGE 1 stimulated cAMP accumulation in a dose-dependent manner. Interestingly, AH6809 significantly attenuated PGE 1-induced cAMP accumulation. Sulprostone, a selective EP3 receptor agonist, induced weak contractions in HCC tissue strips but augmented forskolin-induced cAMP synthesis in HCC SMC. The data in this study suggest that HCC and cultured smooth muscle cells express EP1, EP2 and EP3 receptors. These receptors mediate their responses via different biochemical pathways and are expected to have different responses in regulating smooth muscle tone. Thus, we suggest that the ultimate response in erectile tissue to various prostanoids is the integration of responses elicited by individual EP receptor subtypes to a given ligand.