Alterations in P2X and P2Y purinergic receptor expression in urinary bladder from normal cats and cats with interstitial cystitis

Alterations in P2X and P2Y purinergic receptor expression in urinary bladder from normal cats and cats with interstitial cystitis
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DOI:
10.1152/ajprenal.00118.2004
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发表时间:
2004-11-01
影响因子:
4.2
通讯作者:
Burnstock, G
Burnstock, G
中科院分区:
医学2区
文献类型:
--
作者:
Birder, LA;Ruan, HZ;Burnstock, G

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嘌呤能机制似乎与膀胱的运动和感觉功能有关。传出神经释放的三磷酸腺苷兴奋膀胱平滑肌,而尿路上皮细胞释放的三磷酸腺苷则激活传入神经和尿路上皮细胞。在本研究中,我们用免疫组织化学技术检测了正常猫膀胱尿路上皮、平滑肌和神经中嘌呤受体的分布,以及猫慢性痛性膀胱炎(FIC)时这些受体表达的可能变化。在正常猫中,一系列的P2X受体亚型(P2X(1)、P2X(2)、P2X(3)、P2X(4)、P2X(5)、P2X(6)和P2X(7))和P2Y(P2Y(1)、P2Y(2)和P2Y(4))表达于整个膀胱尿路上皮。在FIC猫中,P2X(1)明显减少,P2Y(2)受体染色消失。在正常猫膀胱中,P2X(3)和P2Y(4)在神经中均有表达,而在FIC中的表达无明显差异。正常膀胱平滑肌未见P2Y受体染色,但有P2X(2)、P2X(1)染色。在FIC膀胱平滑肌中,P2X(1)的表达显著减少。这些发现提出了FIC猫尿路上皮和膀胱平滑肌中的嘌呤能机制发生改变的可能性。由于尿路上皮细胞在膀胱中似乎具有感觉功能,因此尿路上皮嘌呤能受体的可塑性可能与IC的膀胱疼痛症状有关。
Purinergic mechanisms appear to be involved in motor as well as sensory functions in the urinary bladder. ATP released from efferent nerves excites bladder smooth muscle, whereas ATP released from urothelial cells can activate afferent nerves and urothelial cells. In the present study, we used immunohistochemical techniques to examine the distribution of purinoceptors in the urothelium, smooth muscle, and nerves of the normal cat urinary bladder as well as possible changes in the expression of these receptors in cats with a chronic painful bladder condition termed feline interstitial cystitis (FIC) in which ATP release from the urothelium is increased. In normal cats, a range of P2X (P2X(1), P2X(2), P2X(3), P2X(4), P2X(5), P2X(6), and P2X(7)) and P2Y (P2Y(1), P2Y(2), and P2Y(4)) receptor subtypes was expressed throughout the bladder urothelium. In FIC cats, there is a marked reduction in P2X(1) and loss of P2Y(2) receptor staining. Both P2X(3) and P2Y(4) are present in nerves in normal cat bladder, and no obvious differences in staining were detected in FIC. Smooth muscle in the normal bladder did not exhibit P2Y receptor staining but did exhibit P2X ( P2X(2), P2X(1)) staining. In the FIC bladder smooth muscle, there was a significant reduction in P2X(1) expression. These findings raise the possibility that purinergic mechanisms in the urothelium and bladder smooth muscle are altered in FIC cats. Because the urothelial cells appear to have a sensory function in the bladder, it is possible that the plasticity in urothelial purinergic receptors is linked with the painful bladder symptoms in IC.