Department of Pharmacology, School of Medical Sciences, University of New South Wales Sydney, NSW, Australia.
Detrusor Muscle Laboratory, St. George Hospital, University of New South Wales Kogarah, NSW, Australia.
Front Pharmacol. 2013 Nov 28;4:148. doi: 10.3389/fphar.2013.00148. eCollection 2013.
Urothelial cells, myofibroblasts, and smooth muscle cells are important cell types contributing to bladder function. Multiple receptors including muscarinic (M3/M5), tachykinin (NK1/NK2), and purinergic (P2X1/P2Y6) receptors are involved in bladder motor and sensory actions. Using female pig bladder, our aim was to differentiate between various cell types in bladder by genetic markers. We compared the molecular expression pattern between the fresh tissue layers and their cultured cell counterparts. We also examined responses to agonists for these receptors in cultured cells. Urothelial, suburothelial (myofibroblasts), and smooth muscle cells isolated from pig bladder were cultured (10-14 days) and identified by marker antibodies. Gene (mRNA) expression level was demonstrated by real-time PCR. The receptor expression pattern was very similar between suburothelium and detrusor, and higher than urothelium. The gene expression of all receptors decreased in culture compared with the fresh tissue, although the reduction in cultured urothelial cells appeared less significant compared to suburothelial and detrusor cells. Cultured myofibroblasts and detrusor cells did not contract in response to the agonists acetylcholine, neurokinin A, and β,γ-MeATP, up to concentrations of 0.1 and 1 mM. The significant reduction of M3, NK2, and P2X1 receptors under culture conditions may be associated with the unresponsiveness of cultured suburothelial and detrusor cells to their respective agonists. These results suggest that under culture conditions, bladder cells lose the receptors that are involved in contraction, as this function is no longer required. The study provides further evidence that cultured cells do not necessarily mimic the actions exerted by intact tissues.
尿路上皮细胞、肌纤维母细胞和平滑肌细胞是参与膀胱功能的重要细胞类型。多种受体,包括毒蕈碱(M3/M5)、速激肽(NK1/NK2)和嘌呤能(P2X1/P2Y6)受体,参与膀胱运动和感觉作用。本研究使用雌性猪膀胱,旨在通过遗传标记物将膀胱中的各种细胞类型区分开来。我们比较了新鲜组织层与其培养细胞对应物之间的分子表达模式。我们还研究了这些受体激动剂在培养细胞中的反应。从猪膀胱分离的尿路上皮、下尿路上皮(肌纤维母细胞)和平滑肌细胞进行培养(10-14 天),并用标记抗体鉴定。通过实时 PCR 证明基因(mRNA)表达水平。受体表达模式在下尿路上皮和逼尿肌之间非常相似,高于尿路上皮。与新鲜组织相比,所有受体的基因表达在培养中均降低,尽管与下尿路上皮和逼尿肌细胞相比,培养的尿路上皮细胞的减少似乎不那么明显。培养的肌纤维母细胞和逼尿肌细胞对乙酰胆碱、神经激肽 A 和 β,γ-MeATP 等激动剂的反应性没有收缩,最高浓度为 0.1 和 1 mM。培养条件下 M3、NK2 和 P2X1 受体的显著减少可能与培养的下尿路上皮和逼尿肌细胞对各自激动剂无反应有关。这些结果表明,在培养条件下,膀胱细胞失去了参与收缩的受体,因为这种功能不再需要。该研究进一步证明,培养细胞不一定能模拟完整组织所发挥的作用。