Bombesin-related peptides and their receptors: recent advances in their role in physiology and disease states
Bombesin-related peptides and their receptors: recent advances in their role in physiology and disease states
复制标题
DOI：
10.1097/med.0b013e3282f3709b
复制
发表时间：
2008-02-01
影响因子：
3.2
通讯作者：
Jensen, Robert T.
中科院分区：
文献类型：
--
作者：
Gonzalez, Nieves;Moody, Terry W.;Jensen, Robert T.
综述目的哺乳动物铃蟾肽相关肽、胃泌素释放肽和神经调节肽B的作用是由两种受体（BB1-受体、BB2-受体）介导的，这两种受体与孤儿受体BRS-3（BB3-受体）密切相关。本综述的目的是强调对这些肽在生理学/疾病状态的理解方面取得的进展。最近的发现药理学/受体敲除研究表明这些受体参与了许多新的过程/疾病。 Neuromedin B/BB1 受体是垂体-甲状腺功能的重要生理调节因子；调解行为，尤其是恐惧/焦虑；通过与胃泌素释放肽/BB2受体不同的级联介导饱腹感及其自分泌肿瘤生长作用。胃泌素释放肽/BB2 受体在介导瘙痒、肺部发育/损伤、小肠粘膜防御和中枢神经系统过程（例如学习/记忆）的信号中发挥重要作用。其有效生长作用的信号传导机制正在被阐明，并且其可能的治疗靶点正在被确定。 BB3 受体敲除小鼠为了解其肥胖/葡萄糖不耐受提供了见解，并证明该受体可能在肺部对损伤、肿瘤生长和胃肠道运动的反应中发挥重要作用。每种受体在人类肿瘤中经常过度表达，并具有有效的生长作用。人们正在探索这种效应以开发新的抗肿瘤治疗方法，例如与细胞毒性药物缀合的铃蟾肽受体配体。总结该受体家族在生理学和疾病状态中参与越来越多的中枢神经系统/外周过程，并且对其作用的更多了解可能会带来新的治疗方法。
Purpose of reviewMammalian bombesin-related peptides, gastrin-releasing peptide and neuromedin B actions are mediated by two receptors (BB1-receptor, BB2-receptor), which are closely related to the orphan receptor BRS-3 (BB3-receptor). The purpose of this review is to highlight advances in the understanding of these peptides in physiology/disease states.Recent findingsPharmacologic/receptor-knockout studies show involvement of these receptors in a number of new processes/diseases. Neuromedin B/BB1-receptor is an important physiological regulator of pituitary-thyroid function; in mediating behavior, especially feas/anxiety; in mediating satiety through different cascades than gastrin-releasing peptide/BB2 receptors and for its autocrine tumor-growth effects. Gastrin-releasing peptide/BB2-receptor plays important roles in mediating signals for pruritus, lung development/injury, small intestinal mucosal defense, and central nervous system processes such as learning/memory. The signaling mechanisms of its potent growth effects are being elucidated and their possible therapeutic targets identified. BB3-receptor knockout mice provided insights for their obesity/glucose intolerance and demonstrated that this receptor may be important in the lung response to injury, tumor growth and gastrointestinal motility. Each receptor is frequently overexpressed in human tumors and has potent growth effects. This effect is being explored to develop new antitumor treatments, such as bombesin-receptor ligands conjugated to cytotoxic agents.SummaryThis receptor family is involved in an increasing number of central nervous system/peripheral processes physiologically and in disease states, and increased understanding of its role may lead to novel treatments.