Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi-City, Chiba 274-8510, Japan.
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi-City, Chiba 274-8510, Japan.
Life Sci. 2021 Dec 15;287:120130. doi: 10.1016/j.lfs.2021.120130. Epub 2021 Nov 10.
We examined the potential stimulatory effects of U46619 (a prostanoid TP receptor agonist) and five prostanoids on the contractile activities of urinary bladder smooth muscle (UBSM), focusing on the role of the TP receptor and its associated Ca influx routes to understand the roles of prostanoids in the regulation of UB contractile activity.
Changes in the basal tone and spontaneous contractile activity (amplitude and frequency) of isolated guinea pig UBSM were measured isotonically. The presence of TP receptors in UBSM was examined by RT-qPCR and immunofluorescence.
U46619, prostaglandin (PG) E, PGF, and PGA enhanced UBSM basal tone and spontaneous contractile activities, which were measured as amplitudes and frequencies. The enhancing effects of U46619 were completely suppressed by SQ 29,548 (a TP receptor antagonist), which also partially suppressed the stimulating effects of other prostanoids. The expression of TP receptors in UBSMs was verified at the mRNA and protein level. The enhancing effects of U46619 completely disappeared in Ca-free solution. U46619-enhanced basal tone was completely suppressed by verapamil, an inhibitor of voltage-dependent Ca channels (VDCCs), and verapamil strongly decreased the spontaneous contraction frequency. The spontaneous contractions remaining in the presence of verapamil were strongly suppressed by SKF-96365 (an inhibitor of receptor-operated Ca channels (ROCCs)/store-operated Ca channels (SOCCs)), but not by LOE-908 (an inhibitor of ROCCs).
Prostanoids can enhance UBSM contractile activities and thus may be endogenous candidates for induction of detrusor overactivity. The TP receptor and TP-receptor-activated VDCCs/SOCCs are key molecules responsible for these effects.
我们研究了 U46619（前列环素 TP 受体激动剂）和五种前列腺素对膀胱平滑肌（UBSM）收缩活动的潜在刺激作用，重点研究 TP 受体及其相关的 Ca2+内流途径的作用，以了解前列腺素在调节膀胱收缩活动中的作用。
通过等张测量法测量分离的豚鼠 UBSM 的基础张力和自发性收缩活动（幅度和频率）的变化。通过 RT-qPCR 和免疫荧光法检测 UBSM 中 TP 受体的存在。
U46619、前列腺素（PG）E、PGF 和 PGA 增强 UBSM 的基础张力和自发性收缩活动，以幅度和频率来衡量。U46619 的增强作用完全被 SQ 29548（TP 受体拮抗剂）抑制，该拮抗剂也部分抑制了其他前列腺素的刺激作用。TP 受体在 UBSMs 中的表达在 mRNA 和蛋白质水平上得到验证。在无钙溶液中，U46619 的增强作用完全消失。U46619 增强的基础张力完全被维拉帕米（电压依赖性 Ca 通道（VDCCs）抑制剂）抑制，维拉帕米强烈降低自发性收缩频率。维拉帕米存在时残留的自发性收缩被 SKF-96365（受体操作型 Ca 通道（ROCCs）/储存操作型 Ca 通道（SOCCs）抑制剂）强烈抑制，但不受 LOE-908（ROCCs 抑制剂）的影响。
前列腺素可以增强 UBSM 的收缩活动，因此可能是诱导逼尿肌过度活动的内源性候选物。TP 受体和 TP 受体激活的 VDCCs/SOCCs 是负责这些作用的关键分子。
