Capsaicin-induced inhibition of motility of the rat isolated vas deferens: do multiple neuropeptides mediate the visceromotor effects of capsaicin?

Capsaicin-induced inhibition of motility of the rat isolated vas deferens: do multiple neuropeptides mediate the visceromotor effects of capsaicin?
复制标题

辣椒素诱导的大鼠离体输精管运动抑制:多种神经肽是否介导辣椒素的内脏运动作用?

DOI:
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发表时间:
1987
期刊:
Journal of autonomic pharmacology
影响因子:
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通讯作者:
A. Meli
A. Meli
中科院分区:
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文献类型:
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作者:
C. Maggi;S. Giuliani;P. Santicioli;A. Meli

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1.在电场刺激(0.1Hz)和未刺激的大鼠离体输精管上观察了辣椒素的作用,并与辣椒素敏感感觉纤维中储存的神经肽(神经激肽、降钙素基因相关肽(CGRP))的作用进行了比较。2辣椒素(0.01-3 μ M)对场刺激诱发的抽搐产生浓度相关的短暂抑制作用。这种作用的特征在于显著的脱敏,并且在从辣椒素预处理的大鼠(50 mg/kg s.c.,4天前)。神经介导的抽搐幅度不受辣椒素脱敏的影响。3神经激肽(P物质,Kassinin)对神经收缩有增强作用,而CGRP对神经收缩有明显的抑制作用。在Kassinin的存在下,CGRP仍然抑制抽搐,虽然这种抑制作用的时间过程相比,控制延迟。4.在未受刺激的大鼠输精管中,辣椒素(3 μ M)和CGRP(0.1 μ M)都没有任何显著的运动效应。然而,当先前暴露于卡西宁(0.2 μ M)引发阶段性收缩时,辣椒素(3 μ M)或CGRP(10-100 nM)都具有迅速的抑制作用。辣椒素的抑制表现出明显的脱敏作用,而辣椒素脱敏后CGRP的作用仍然明显。5辣椒素或CGRP对Kassinin刺激的大鼠离体输精管节律性收缩的抑制作用不受先前暴露于河豚毒素(0.5 μ M)的影响。6在4 ℃下保存24小时,大鼠离体输精管对神经刺激的反应降低65%。残余反应是河豚毒素敏感的,并且可以被Kassinin(0.2 μ M)增强或被CGRP(10-100 nM)抑制,如在对照中观察到的。在这些制剂中,与对照相比,辣椒素(3 μ M)的抑制作用显著降低(约等于50%),并且在一些制剂中被消除。这些发现表明,在大鼠离体输精管中存在辣椒素敏感的感觉神经支配,在化学刺激时,通过河豚毒素不敏感的机制释放一种物质,该物质在连接后水平抑制运动。CGRP是一个可能的候选人的辣椒素敏感的神经末梢释放的抑制性感觉递质的作用,在这个准备。
1 The effects of capsaicin have been investigated in the field-stimulated (0.1 Hz) or unstimulated rat isolated vas deferens and compared with those of some neuropeptides (neurokinins, calcitonin gene-related peptide (CGRP) putatively stored in capsaicin-sensitive sensory fibres. 2 Capsaicin (0.01-3 microM) produced a concentration-related transient inhibition of the field-stimulation-induced twitches. This effect was characterized by marked desensitization and could not be elicited in preparations excised from capsaicin-pretreated rats (50 mg/kg s.c., 4 days before). The amplitude of the nerve-mediated twitches was unaffected by capsaicin-desensitization. 3 Neurokinins (substance P, Kassinin) produced a potentiation of the nerve-mediated contractions while CGRP had a potent inhibitory effect. In the presence of Kassinin, CGRP still inhibited twitches although the time course of this inhibitory effect was delayed as compared to controls. 4 In the unstimulated rat vas deferens neither capsaicin (3 microM) nor CGRP (0.1 microM) had any significant motor effect. However, when phasic contractions were initiated by previous exposure to Kassinin (0.2 microM), both capsaicin (3 microM) or CGRP (10-100 nM) had a prompt inhibitory effect. Capsaicin inhibition exhibited a marked desensitization while the effect of CGRP was still evident after capsaicin-desensitization. 5 The inhibitory effect of capsaicin or CGRP on the Kassinin-stimulated rhythmic contractions of the rat isolated vas deferens was unaffected by a previous exposure to tetrodotoxin (0.5 microM). 6 Storage at 4 degrees C for 24 h produced a 65% reduction of the response of the rat isolated vas deferens to nerve-stimulation. The residual response was tetrodotoxin-sensitive and could be potentiated by Kassinin (0.2 microM) or inhibited by CGRP (10-100 nM) as observed in controls. In these preparations the inhibitory effect of capsaicin (3 microM) was significantly reduced (approximately equal to 50%) and in some preparations abolished, as compared to controls. 7 These findings indicate the existence, in the rat isolated vas deferens, of capsaicin-sensitive sensory innervation which, upon chemical stimulation, releases, through a tetrodotoxin-insensitive mechanism, a substance(s) which inhibits motility at postjunctional level. CGRP is a possible candidate for the role of inhibitory sensory transmitter released from capsaicin-sensitive nerve endings in this preparation.