Urogenix Inc./Astellas, 801 Capitola Dr., Durham, NC, USA.
Neuropeptides. 2013 Oct;47(5):305-13. doi: 10.1016/j.npep.2013.08.003. Epub 2013 Sep 5.
Bombesin receptors (BB receptors) and/or bombesin related peptides are expressed in the lower urinary tract, though their function and distribution in different species is largely unknown. This study examines whether BB receptor agonists can contract bladder smooth muscle in rats, mice, pigs and humans.
Bladder strips were placed in tissue baths for in vitro contractility. Neuronally evoked contractions were elicited using electric field stimulation (EFS). Effects of the BB receptor agonists, neuromedin B (NMB; BB1 receptor agonist) and gastrin-releasing peptide (GRP; BB2 receptor agonist) on baseline tone and EFS-induced contractions were monitored.
In rat and human bladder strips, NMB and GRP (10(-11)-10(-6)M) increased EFS-induced contractions in a concentration dependent manner. In these species, NMB and GRP also increased baseline tension. In mouse and pig bladder strips, NMB and GRP (10(-8)-3×10(-6)M) had no effects on either parameter.
These data suggest that bombesin receptors BB receptor 1 and/or BB receptor 2 increase bladder contractions in rat and human. The site of action of these receptors may be pre- and/or post-synaptic, increasing release of transmitters or enhancing smooth muscle excitability, respectively. Thus, BB1 receptor and/or BB2 receptor may offer therapeutic targets for voiding dysfunction associated with impaired bladder contractility; however, species differences must be considered when studying these receptors. Part of this work was published in an abstract form at the SFN meeting New Orleans, 2012.
铃蟾肽受体(BB 受体)和/或铃蟾肽相关肽在下尿路表达,尽管其在不同物种中的功能和分布尚不清楚。本研究旨在研究 BB 受体激动剂是否能引起大鼠、小鼠、猪和人膀胱平滑肌收缩。
将膀胱条置于组织浴槽中进行体外收缩性研究。使用电刺激(EFS)诱发神经源性收缩。监测 BB 受体激动剂神经降压素 B(NMB;BB1 受体激动剂)和胃泌素释放肽(GRP;BB2 受体激动剂)对基础张力和 EFS 诱导收缩的影响。
在大鼠和人膀胱条中,NMB 和 GRP(10(-11)-10(-6)M)以浓度依赖的方式增加 EFS 诱导的收缩。在这些物种中,NMB 和 GRP 也增加了基础张力。在小鼠和猪膀胱条中,NMB 和 GRP(10(-8)-3×10(-6)M)对这两个参数均无影响。
这些数据表明,铃蟾肽受体 BB 受体 1 和/或 BB 受体 2 增加了大鼠和人膀胱的收缩。这些受体的作用部位可能是突触前和/或突触后,分别增加递质释放或增强平滑肌兴奋性。因此,BB1 受体和/或 BB2 受体可能成为与膀胱收缩功能障碍相关的排尿功能障碍的治疗靶点;然而,在研究这些受体时必须考虑物种差异。这项工作的一部分已在 2012 年新奥尔良 SFN 会议的摘要中发表。