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首页> 外文期刊>Life sciences >Modulation of TRPV1-dependent contractility of normal and diabetic bladder smooth muscle by analgesic toxins from sea anemone Heteractis crispa
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Modulation of TRPV1-dependent contractility of normal and diabetic bladder smooth muscle by analgesic toxins from sea anemone Heteractis crispa

机译：海葵异丝桃的镇痛毒素对正常和糖尿病膀胱平滑肌TRPV1依赖性收缩力的调节

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Aims: TRPV1-expressing, capsaicin (CAP)-sensitive afferent fibers innervating bladder in addition to sensory function also exhibit efferent features consisting in TRPV1-dependent release of tachykinins (TAC) affecting detrusor smooth muscle (DSM) contractions. Our aim was to investigate the effects of two novel polypeptide inhibitors of TRPV1 from the venom of tropical sea anemone Heteractis crispa, APHC1 and APHC3, on the contractions of DSM from bladders of normal and diabetic rats. Main methods: Experiments were conducted on urothelium-devoid DSM strips from normal rats and rats 8 weeks after streptozotocin-induced diabetes by means of contraction force measurements. Key findings: Pre-exposure of DSM strips to APHC1 or APHC3 (200 nM) specifically inhibited CAP-induced, TRPV1-dependent contractions. Both peptides also transiently enhanced basal tone and spontaneous contractions of DSM strips followed by delayed suppression of electric field stimulation (EFS)-evoked nonadrenergic-noncholinergic (NANC) contractions. The decrease of the amplitude of EFS-evoked NANC contractions by APHC1 or APHC3 reached 38.5 ± 3.4% and 25.1 ± 1.6%, respectively, in normal DSM strips and 46.3 ± 3.3% and 43.9 ± 1.8%, respectively, in diabetic ones. APHC-peptide-induced transient enhancement of basal tone could be mimicked by serine protease inhibitor, 4-(2-aminoethyl)bezenesulfonyl fluoride (300 μM). Significance: Our results demonstrate that APHC1 and APHC3 may be considered as effective inhibitors of bladder contractility especially during diabetic cystopathy. Modality of action of APHC-polypeptides via the mechanisms involving decreased TRPV1-dependent release of TAC from bladder afferents and suppression of TAC degradation due to their activity as endogenous proteases inhibitors is proposed.
机译：目的：表达TRPV1的辣椒素（CAP）敏感的传入神经支配膀胱，除了感觉功能外，还具有传出特征，包括依赖TRPV1的速激肽（TAC）释放，影响逼尿肌平滑肌（DSM）收缩。我们的目的是研究两种新的热带海葵异纤菌蛇毒蛇毒TRPV1多肽抑制剂APHC1和APHC3对正常和糖尿病大鼠膀胱DSM收缩的影响。主要方法：通过收缩力测量，对正常大鼠和链脲佐菌素诱发的糖尿病后8周大鼠的无尿路上皮DSM条进行了实验。主要发现：将DSM胶条预先暴露于APHC1或APHC3（200 nM）会特异性抑制CAP诱导的TRPV1依赖性收缩。两种肽还可以瞬时增强DSM条带的基调和自发收缩，然后延迟抑制电场刺激（EFS）引起的非肾上腺素能非胆碱能（NANC）收缩。在正常的DSM试纸中，APHC1或APHC3引起的EFS诱发的NANC收缩幅度下降分别达到38.5±3.4％和25.1±1.6％，在糖尿病患者中分别达到46.3±3.3％和43.9±1.8％。丝氨酸蛋白酶抑制剂4-（2-氨乙基）苯磺酰氟（300μM）可以模仿APHC肽诱导的基础基调的瞬时增强。意义：我们的结果表明，APHC1和APHC3可以被认为是有效的膀胱收缩抑制剂，尤其是在糖尿病性膀胱病期间。提出了经由减少TRPV1依赖性TAC从膀胱传入细胞释放TAC以及由于其作为内源蛋白酶抑制剂的活性而抑制TAC降解的机制，APHC多肽的作用方式。

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