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新生大鼠经辣椒素处理进行感觉去神经支配后膀胱和输精管的收缩性

Contractility of urinary bladder and vas deferens after sensory denervation by capsaicin treatment of newborn rats.

作者信息

Ziganshin A U, Ralevic V, Burnstock G

机构信息

Department of Anatomy and Developmental Biology, University College London.

出版信息

Br J Pharmacol. 1995 Jan;114(1):166-70. doi: 10.1111/j.1476-5381.1995.tb14921.x.

Abstract
  1. Capsaicin, a selective sensory neurotoxin, was given to newborn rats and at the age of 3 months the contractile activity of the urinary bladder detrusor muscle and vas deferens evoked by either electrical field stimulation (EFS) or exogenous adenosine 5'-triphosphate (ATP) and carbachol (urinary bladder), or ATP and noradrenaline (vas deferens) were tested. 2. EFS of the urinary bladder evoked contractions which consisted of cholinergic and purinergic components, since they could be partially blocked by either the muscarinic cholinoceptor antagonist, atropine (0.3 microM) or by desensitization of P2x-purinoceptors with alpha,beta-methylene ATP (10 microM). In capsaicin-treated rats, contractions of the urinary bladder evoked by EFS were significantly larger than those of control (vehicle-treated) animals, and this difference remained after the purinergic component of the contractions was blocked by desensitization of P2x-purinoceptors with alpha,beta-methylene ATP. However, when the cholinergic component of the contractions was blocked with atropine, the difference between the groups at 8 Hz and 16 Hz was abolished; EFS caused significantly larger contractions of the capsaicin-treated rat bladder only at frequencies of 2 Hz and 4 Hz. 3. EFS evoked contractions of the vas deferens consisted of adrenergic and purinergic components since they could be partially blocked by either the alpha-adrenoceptor antagonist, phentolamine (3 microM) or by alpha,beta-methylene ATP (10 microM). The contractions of the vas deferens were significantly larger than in the capsaicin-treated rats only at a frequency of 16 Hz. There were no differences between vas deferens contractions of the two groups either after desensitization of P2X-purinoceptors by alpha,beta-methylene ATP or in the presence of phentolamine.4. Contractions of the capsaicin-treated rat urinary bladder evoked by exogenous carbachol (0.1-100 microM) were not significantly different from those of controls, the pD2 values being 1.78 +/- 0.23 micro M and 1.90 +/- 0.20 micro M respectively. There was also no significant difference between the groups in contractions of the bladder evoked by ATP (10 micro M-3 mM).5. Contractions of the vas deferens evoked by either ATP (10 micro M-3 mM) or noradrenaline (1-1000 micro M) in the capsaicin-treated group showed no significant difference between control and capsaicin treated rats.6. In conclusion, the present results indicate that chronic capsaicin treatment increases the amplitude of contractions of the rat urinary bladder, an effect which preferentially involves the cholinergic component of the response; since the response to carbachol is unaffected, the change involves prejunctional mechanisms. In contrast, both the purinergic and adrenergic components of contraction in the vas deferens are unaffected by capsaicin. It is suggested that sensory nerves have a trophic influence on the development of parasympathetic nerves in the rat bladder; removal of sensory nerves shortly after birth results in an increase mainly in the cholinergic, and to a lesser extent purinergic component.
摘要
  1. 将选择性感觉神经毒素辣椒素给予新生大鼠,在3个月龄时,测试电场刺激(EFS)或外源性5'-三磷酸腺苷(ATP)和卡巴胆碱(膀胱),或ATP和去甲肾上腺素(输精管)诱发的膀胱逼尿肌和输精管的收缩活性。2. 膀胱的EFS诱发的收缩由胆碱能和嘌呤能成分组成,因为它们可被毒蕈碱胆碱受体拮抗剂阿托品(0.3微摩尔)或用α,β-亚甲基ATP(10微摩尔)使P2x嘌呤受体脱敏而部分阻断。在辣椒素处理的大鼠中,EFS诱发的膀胱收缩明显大于对照(载体处理)动物,在用α,β-亚甲基ATP使收缩的嘌呤能成分脱敏后,这种差异仍然存在。然而,当用阿托品阻断收缩的胆碱能成分时,8赫兹和16赫兹时两组之间的差异消失;EFS仅在2赫兹和4赫兹频率下引起辣椒素处理的大鼠膀胱明显更大的收缩。3. 输精管的EFS诱发的收缩由肾上腺素能和嘌呤能成分组成,因为它们可被α-肾上腺素能受体拮抗剂酚妥拉明(3微摩尔)或α,β-亚甲基ATP(10微摩尔)部分阻断。输精管的收缩仅在16赫兹频率下明显大于辣椒素处理的大鼠。在用α,β-亚甲基ATP使P2X嘌呤受体脱敏后或在酚妥拉明存在下,两组输精管收缩之间没有差异。4. 外源性卡巴胆碱(0.1 - 100微摩尔)诱发的辣椒素处理的大鼠膀胱收缩与对照无明显差异,pD2值分别为1.78±0.23微摩尔和1.90±0.20微摩尔。ATP(10微摩尔 - 3毫摩尔)诱发的膀胱收缩在两组之间也没有显著差异。5. 辣椒素处理组中ATP(10微摩尔 - 3毫摩尔)或去甲肾上腺素(1 - 1000微摩尔)诱发的输精管收缩在对照和辣椒素处理的大鼠之间没有显著差异。6. 总之,目前的结果表明,慢性辣椒素处理增加了大鼠膀胱收缩的幅度,这种效应优先涉及反应的胆碱能成分;由于对卡巴胆碱的反应未受影响,这种变化涉及节前机制。相比之下,输精管收缩的嘌呤能和肾上腺素能成分均不受辣椒素影响。有人提出,感觉神经对大鼠膀胱副交感神经的发育具有营养作用;出生后不久去除感觉神经主要导致胆碱能成分增加,嘌呤能成分增加程度较小。

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