de Vente J, Markerink-van Ittersum M, Gillespie J I
European Graduate School of Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University, The Netherlands.
J Urol. 2007 Mar;177(3):1191-4. doi: 10.1016/j.juro.2006.10.039.
We examined the localization of natriuretic peptide responsive, cyclic guanosine monophosphate producing cells in the guinea pig bladder.
The bladder was removed from male guinea pigs sacrificed by cervical dislocation. The lateral wall of the bladder was cut into strips 2 mm thick. The tissue pieces were incubated in the presence of human atrial natriuretic peptide, rat brain natriuretic peptide and C-type natriuretic peptide or the nitric oxide donor DEANO (diethylamine NONOate or 1,1-diethyl-2-hydroxy-2-nitrosohydrazine) (Sigma). Cyclic guanosine monophosphate immunoreactivity was localized using an antibody against formaldehyde fixed cyclic guanosine monophosphate.
Atrial natriuretic peptide and brain natriuretic peptide stimulated cyclic guanosine monophosphate synthesis in suburothelial interstitial cells, whereas C-type natriuretic peptide was not effective. In contrast, DEANO stimulated cyclic guanosine monophosphate synthesis in urothelial umbrella cells, suburothelial interstitial cells, muscle interstitial cells and neurons. The effect of atrial natriuretic peptide and brain natriuretic peptide was not inhibited by ODQ (1H-[1, 2, 4]oxadiazolo[4-3a]quinoxalin-1-one), an inhibitor of nitric oxide responsive soluble guanylyl cyclase.
To our knowledge our findings show for the first time a localized effect of atrial natriuretic peptide and brain natriuretic peptide to the suburothelial cells of the guinea pig bladder. These cells express the soluble guanylyl cyclase and particulate guanylyl cyclase-A isoforms. The specific physiological role of these cells is not known but it was suggested that they may be involved in the generation or modulation of sensation. The results imply a role for natriuretic peptide-cyclic guanosine monophosphate signaling in the processing of sensory information in the bladder.
我们研究了豚鼠膀胱中利钠肽反应性、产生环磷酸鸟苷的细胞的定位。
从经颈椎脱臼处死的雄性豚鼠身上取出膀胱。将膀胱侧壁切成2毫米厚的条带。组织块在人心房利钠肽、大鼠脑利钠肽和C型利钠肽或一氧化氮供体DEANO(二乙胺NONOate或1,1 - 二乙基 - 2 - 羟基 - 2 - 亚硝基肼)(西格玛)存在的情况下孵育。使用针对甲醛固定的环磷酸鸟苷的抗体对环磷酸鸟苷免疫反应性进行定位。
心房利钠肽和脑利钠肽刺激了膀胱上皮下间质细胞中环磷酸鸟苷的合成,而C型利钠肽无效。相比之下,DEANO刺激了膀胱上皮伞细胞、膀胱上皮下间质细胞、肌肉间质细胞和神经元中环磷酸鸟苷的合成。一氧化氮反应性可溶性鸟苷酸环化酶的抑制剂ODQ(1H - [1,2,4]恶二唑并[4,3 - a]喹喔啉 - 1 - 酮)并未抑制心房利钠肽和脑利钠肽的作用。
据我们所知,我们的研究结果首次表明心房利钠肽和脑利钠肽对豚鼠膀胱上皮下细胞有局部作用。这些细胞表达可溶性鸟苷酸环化酶和颗粒性鸟苷酸环化酶 - A亚型。这些细胞的具体生理作用尚不清楚,但有人认为它们可能参与感觉的产生或调节。结果表明利钠肽 - 环磷酸鸟苷信号传导在膀胱感觉信息处理中起作用。