Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University.
Biol Pharm Bull. 2024;47(9):1467-1476. doi: 10.1248/bpb.b24-00440.
Since its first discovery as a bioactive phospholipid inducing potent platelet aggregation, platelet-activating factor (PAF) has been shown to be involved in a wide variety of inflammatory and allergic disease states. Many pharmacological studies in the 1980s and 1990s also showed that PAF induces endothelium-dependent vascular relaxation and contraction of various smooth muscles (SMs), including those in the airway, gastrointestinal organs, and uterus. However, since the late 1990s, there have been few reports on the SM contractions induced by PAF. The lower urinary tract (LUT), particularly the urinary bladder (UB) has attracted recent attention in SM pharmacology research because patients with LUT dysfunctions including overactive bladder are increasing as the population ages. In addition, recent clinical studies have implicated the substantial role of PAF in the inflammatory state in LUT because its production increases with smoking and with cancer. However, the effects of PAF on mechanical activities of LUT SMs including UBSM have not been investigated to date. Recently, we found that PAF very strongly increased mechanical activities of UBSM in guinea pigs and mice, and partly elucidated the possible mechanisms underlying these actions of PAF. In this review, we describe the effects of PAF on LUT SMs by introducing our recent findings obtained in isolated UBSMs and discuss the physiological and pathophysiological significance. We also introduce our data showing the effects of PAF on the SM mechanical activities of genital tissues (prostate and vas deferens).
自首次发现作为一种具有强大血小板聚集作用的生物活性磷脂以来,血小板激活因子 (PAF) 已被证明参与了多种炎症和过敏疾病状态。20 世纪 80 年代和 90 年代的许多药理学研究还表明,PAF 可诱导内皮依赖性血管舒张和各种平滑肌 (SM) 的收缩,包括气道、胃肠道器官和子宫中的 SM。然而,自 20 世纪 90 年代末以来,关于 PAF 诱导的 SM 收缩的报道很少。下尿路 (LUT),特别是膀胱 (UB),在 SM 药理学研究中最近受到关注,因为随着人口老龄化,LUT 功能障碍(包括膀胱过度活动症)的患者正在增加。此外,最近的临床研究表明 PAF 在 LUT 的炎症状态中起重要作用,因为其产生随着吸烟和癌症而增加。然而,迄今为止,尚未研究 PAF 对包括 UBSM 在内的 LUT SM 机械活动的影响。最近,我们发现 PAF 非常强烈地增加了豚鼠和小鼠 UBSM 的机械活动,并部分阐明了 PAF 这些作用的可能机制。在这篇综述中,我们通过介绍我们在分离的 UBSM 中获得的最新发现来描述 PAF 对 LUT SM 的影响,并讨论其生理和病理生理意义。我们还介绍了我们的数据,这些数据显示了 PAF 对生殖组织(前列腺和输精管)SM 机械活动的影响。