Jankowski V, Karadogan S, Vanholder R, Nofer J-R, Herget-Rosenthal S, van der Giet M, Tölle M, Tran T N A, Zidek W, Jankowski J
Charité, Medizinische Klinik IV (CBF), Berlin, Germany.
Kidney Int. 2007 May;71(10):994-1000. doi: 10.1038/sj.ki.5002186. Epub 2007 Mar 14.
The purinergic receptor system plays an important role in the regulation of both vascular and tubular functions within the kidney; however, the release of purinergic agonists other than ATP by renal tissue is not known. In this investigation, we determine if kidney tissue is a source of diadenosine polyphosphates, which have high affinity for the P(2X) and P(2Y) receptors. Both diadenosine pentaphosphate and hexaphosphate were identified by matrix-assisted laser desorption ionization-mass spectrometry in extracts purified from both whole porcine kidney and from cloned cells of the LLC-PK1 cell line. Both polyphosphates in nanomolar concentrations were found to significantly stimulate the proliferation of vascular smooth muscle cells derived from rat thoracic aortas. The purinergic-receptor antagonist, suramin, did not significantly affect the growth-stimulatory properties of the polyphosphates. The growth stimulation of vascular smooth muscle cells by platelet-derived growth factor was potentiated by both diadenosine polyphosphates. We conclude that diadenosine polyphosphates are endogenous purinergic agonists of the kidney that have physiologic and pathophysiologic relevance. These epithelial cell metabolic products have vasoregulatory properties while linking the energy supply and tubular function.
嘌呤能受体系统在调节肾脏内血管和肾小管功能方面发挥着重要作用;然而,肾组织释放的除ATP之外的嘌呤能激动剂尚不清楚。在本研究中,我们确定肾组织是否是对P(2X)和P(2Y)受体具有高亲和力的多磷酸二腺苷的来源。通过基质辅助激光解吸电离质谱法在从整个猪肾和LLC-PK1细胞系的克隆细胞中纯化的提取物中鉴定出了五磷酸二腺苷和六磷酸二腺苷。发现纳摩尔浓度的两种多磷酸盐均能显著刺激源自大鼠胸主动脉的血管平滑肌细胞的增殖。嘌呤能受体拮抗剂苏拉明对多磷酸盐的生长刺激特性没有显著影响。两种多磷酸二腺苷均增强了血小板衍生生长因子对血管平滑肌细胞的生长刺激作用。我们得出结论,多磷酸二腺苷是肾脏的内源性嘌呤能激动剂,具有生理和病理生理相关性。这些上皮细胞代谢产物具有血管调节特性,同时连接能量供应和肾小管功能。