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猪膀胱尿路上皮/固有层的非肾上腺素能、非胆碱能、非嘌呤能收缩

Non-adrenergic, non-cholinergic, non-purinergic contractions of the urothelium/lamina propria of the pig bladder.

作者信息

Moro C, Chess-Williams R

机构信息

Faculty of Health Sciences and Medicine, Bond University, Queensland, 4229, Australia.

出版信息

Auton Autacoid Pharmacol. 2012 Oct;32(3 Pt 4):53-9. doi: 10.1111/aap.12000.

DOI:10.1111/aap.12000
PMID:22994938
Abstract

Acetylcholine, and to a lesser extent ATP, mediates neurogenic contractions of bladder smooth muscle. Recently, the urothelium and lamina propria have also been shown to have contractile properties, but the neurotransmitters involved in mediating responses to nerve stimulation have not been investigated. Isolated strips of porcine urothelium with lamina propria were electrically field stimulated and contractions recorded. Drugs interfering with neurotransmission were then employed to identify which neurotransmitters mediated responses. Strips of urothelium/lamina propria developed spontaneous contractions with a frequency of 3.5±0.1 cycles min⁻¹ and amplitude of 0.84±0.06 g. Electrical field stimulation at 5, 10, and 20 Hz resulted in frequency-related contractions (1.13±0.36 g, 1.59±0.46 g and 2.20±0.53 g, respectively, n=13), and these were reduced in the presence of tetrodotoxin (1 μm) by 77±20% at 5 Hz, 79±7% at 10 Hz and 74±12% at 20 Hz (all P<0.01), indicating they were predominantly neurogenic in nature. Neither the muscarinic antagonist atropine (10 μm), the adrenergic neurone blocker guanethidine (10 μm) nor desensitization of the purinergic receptors with α,β-methylene ATP (10 μm) affected the contractile amplitude. Similarly, responses were not affected by the nitric oxide synthase inhibitor L-NNA (100 μm) or drugs that interfere with peptide neurotransmission (capsaicin, NK2 antagonist GR159897, protease inhibitors). In conclusion, electrical depolarization of the nerves present in the porcine urothelium/lamina propria results in frequency-dependent contractions, which are predominantly neurogenic in nature. These contractions are resistant to drugs that inhibit the adrenergic, cholinergic and purinergic systems. The neurotransmitter involved in the responses of this tissue is therefore unknown but does not appear to be a peptide.

摘要

乙酰胆碱,以及程度较轻的三磷酸腺苷(ATP),介导膀胱平滑肌的神经源性收缩。最近,尿路上皮和固有层也被证明具有收缩特性,但介导对神经刺激反应的神经递质尚未得到研究。用电场刺激分离出的带有固有层的猪尿路上皮条,并记录收缩情况。然后使用干扰神经传递的药物来确定哪些神经递质介导反应。尿路上皮/固有层条出现自发收缩,频率为3.5±0.1次/分钟,幅度为0.84±0.06克。5、10和20赫兹的电场刺激导致频率相关的收缩(分别为1.13±0.36克、1.59±0.46克和2.20±0.53克,n = 13),在存在河豚毒素(1微摩尔)的情况下,5赫兹时收缩减少77±20%,10赫兹时减少79±7%,20赫兹时减少74±12%(所有P<0.01),表明它们主要是神经源性的。毒蕈碱拮抗剂阿托品(10微摩尔)、肾上腺素能神经元阻滞剂胍乙啶(10微摩尔)或用α,β-亚甲基ATP(10微摩尔)使嘌呤能受体脱敏均不影响收缩幅度。同样,一氧化氮合酶抑制剂L-NNA(100微摩尔)或干扰肽类神经传递的药物(辣椒素、NK2拮抗剂GR159897、蛋白酶抑制剂)也不影响反应。总之,猪尿路上皮/固有层中存在的神经的电去极化导致频率依赖性收缩,这些收缩主要是神经源性的。这些收缩对抑制肾上腺素能、胆碱能和嘌呤能系统的药物有抗性。因此,参与该组织反应的神经递质尚不清楚,但似乎不是一种肽。

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