Induction of bradykinin B1 receptors in rat colonic epithelium
Induction of bradykinin B1 receptors in rat colonic epithelium
复制标题
大鼠结肠上皮缓激肽 B1 受体的诱导
DOI：
--
复制
发表时间：
1997
影响因子：
7.3
通讯作者：
A. Cuthbert
中科院分区：
文献类型：
--
作者：
Sarah Teather;A. Cuthbert
Des‐Arg9缓激肽（DAB）是一种经典的B1‐激肽受体激动剂，应用于大鼠离体结肠上皮基底外侧表面时没有效果。组织分离后3小时，DAB引起的延迟长达2分钟后，短路电流（SCC）持续增加。在体外放置3小时后，DAB引起的结肠上皮细胞SCC升高是由于电致氯离子分泌，因为电流升高被氟塞胺逆转，并且在没有囊性纤维化跨膜传导调节剂（CFTR）氯离子通道的情况下不会发生。DAB的EC50约为50 nM。转录抑制剂（放线菌素D）和翻译抑制剂（环己亚胺）阻止DAB敏感性的出现，而不影响对另一种促分泌剂（福斯克林）的反应。经典的B1‐激肽受体拮抗剂，Leu8‐des‐Arg9缓激肽，在大鼠结肠上皮中被证明是一种激动剂。其他B1‐激肽受体拮抗剂（des‐Arg10‐Hoe 140和R‐715）抑制“衰老”结肠上皮细胞对DAB的反应，并且通过增加DAB浓度很容易克服这种抑制。对DAB的反应似乎不涉及任何显著程度的前列腺素、白三烯、组胺或一氧化氮的形成。此外，在剥离的结肠制备中没有明显的神经元受累。远端结肠不同部位的上皮细胞对DAB的反应无显著差异。讨论了结肠上皮对B1 -和B2 -激肽受体激动剂反应的差异。
Des‐Arg9 bradykinin (DAB), a classical B1‐kinin receptor agonist was without effect when applied to the basolateral surface of rat isolated colon epithelium. Three hours after tissues were isolated DAB caused, after a delay of up to 2 min, a maintained increase of short circuit current (SCC). The SCC increase in colonic epithelia, mounted in vitro for three hours, caused by DAB was due to electrogenic chloride secretion as the current increase was reversed by frusemide and did not occur in the absence of cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels. The EC50 for DAB was approximately 50 nM. An inhibitor of transcription (actinomycin D) and of translation (cycloheximide) prevented the appearance of DAB sensitivity without affecting the responses to another secretagogue (forskolin). The classical B1‐kinin receptor antagonist, Leu8‐des‐Arg9 bradykinin, was shown to be an agonist in rat colon epithelium. Other B1‐kinin receptor antagonists (des‐Arg10‐Hoe 140 and R‐715) inhibited the responses to DAB in ‘aged’ colonic epithelia, and the inhibition was easily surmounted by increasing the concentration of DAB. Response to DAB did not appear to involve to any significant extent, the formation of prostaglandins, leukotrienes, histamine or nitric oxide. Furthermore, no neuronal involvement was apparent in the stripped colonic preparations. The responses to DAB were not significantly different in epithelia taken from different parts of the distal colon. The differences between the responses of the colonic epithelium to B1‐ and B2‐kinin receptor agonists are discussed.