The inhibitory modulation of guinea-pig intestinal peristalsis caused by capsaicin involves calcitonin gene-related peptide and nitric oxide
The inhibitory modulation of guinea-pig intestinal peristalsis caused by capsaicin involves calcitonin gene-related peptide and nitric oxide
复制标题
辣椒素对豚鼠肠道蠕动的抑制作用涉及降钙素基因相关肽和一氧化氮
DOI：
10.1007/bf00168922
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
P. Holzer
中科院分区：
文献类型：
--
作者：
L. Barthó;P. Holzer
研究了辣椒素刺激豚鼠离体回肠传入神经元对肠蠕动的影响及可能参与这一作用的神经介质。引起蠕动波的腔内压力阈值用于量化蠕动的促进（阈值降低）或抑制（阈值增加）。辣椒素（0.1-1 μM）引起最初的短期蠕动刺激，随后是长期的蠕动活性抑制。3.3 μM辣椒素预处理后，1 μM辣椒素对肠段无效，表明该药物具有传入神经元依赖性作用。相反，高浓度辣椒素（33 μM）引起的蠕动的消除在去除时是完全可逆的，并且在再给辣椒素时是可重复的，这是平滑肌兴奋性非特异性抑制的特征。速激肽NK1受体拮抗剂(+)-(2S, 3S)-3-（2-甲氧基苄基氨基）-2-苯基哌啶（CP-99,994; 0.3 μM）和速激肽NK2受体拮抗剂L(-)- n -甲基- n[4-乙酰氨基-4-苯基哌啶-2-（3,4-二氯苯基）丁基]-苯酰胺（SR-48,968; 0.1 μM）联合使用时，基线蠕动和辣椒素（1 μM）对蠕动的兴奋/抑制作用保持不变。进一步的实验，在低浓度的阿托品（10 nM）存在下进行，表明catcitonin基因相关肽（CGRP）拮抗人α-catcitonin基因相关肽（8-37）[hCGRP (8-37)]；10 μM]可以减弱辣椒素对蠕动的延迟抑制作用，但不影响基线蠕动活性和辣椒素诱导的蠕动促进作用。ng -硝基-l-精氨酸甲基lester （l-NAME, 300 μM）阻断一氧化氮（NO）的合成，促进了基线蠕动活性，减少了辣椒素（1 μM）引起的延迟蠕动抑制，而不影响辣椒素的初始蠕动刺激作用。l-NAME的作用被l-精氨酸（1mm）阻断。目前的研究数据表明，辣椒素敏感的传入神经元不参与豚鼠小肠中为蠕动服务的神经通路，而是在辣椒素刺激下调节蠕动活动。辣椒素对蠕动的初始刺激作用独立于通过NK1或NK2受体作用的速激素，而辣椒素诱导的延迟性蠕动抑制涉及CGRP和NO。
The effect of capsaicin-induced stimulation of afferent neurons on peristalsis and the possible neural mediators involved in this action were examined in the guinea-pig isolated ileum. The intraluminal pressure threshold for eliciting peristaltic waves was used to quantify facilitation (decrease in threshold) or inhibition (increase in threshold) of peristalsis. Capsaicin (0.1–1 μM) caused an initial short-lasting stimulation of peristalsis followed by a prolonged inhibition of peristaltic activity. Capsaicin (1 μM) was ineffective when the gut segments had been pretreated with 3.3 μM capsaicin, which is indicative of an afferent neuron-dependent action of the drug. In contrast, the abolition of peristalsis caused by a high concentration of capsaicin (33 μM) was fully reversible on removal and reproducible on readministration of capsaicin, a feature characteristic of a nonspecific depression of smooth muscle excitability. Baseline peristalsis and the excitatory/inhibitory effect of capsaicin (1 μM) on peristalsis remained unaltered by a combination of the tachykinin NK1 receptor antagonist ( + )-(2S, 3S)-3-(2-methoxybenzylamino)-2-phenyl piperidine (CP-99,994; 0.3 μM) and the tachykinin NK2 receptor antagonist L(-)-N-methyl-N[4-acetylamino-4-phenyl-piperidino-2-(3,4-dichlorophenyl)butyl]-benzamide (SR-48,968; 0.1 μM). Further experiments, performed in the presence of a low concentration of atropine (10 nM) showed that the catcitonin gene-related peptide (CGRP) antagonist human α-catcitonin gene-related peptide (8–37) [hCGRP (8–37); 10 μM] attenuated the delayed inhibitory effect of capsaicin on peristalsis, but did not influence baseline peristaltic activity and the capsaicin-induced facilitation of peristalsis. Blockade of nitric oxide (NO) synthesis by NG-nitro-l-arginine methylester (l-NAME, 300 μM) facilitated baseline peristaltic activity and reduced the delayed inhibition of peristalsis caused by capsaicin (1 μM) without affecting the initial peristalsis-stimulating action of capsaicin. The effects of l-NAME were prevented by l-arginine (1 mM). The data of the current study indicate that capsaicin-sensitive afferent neurons do not participate in the neural pathways subserving peristalsis in the guinea-pig small intestine, but modulate peristaltic activity upon stimulation with capsaicin. The initial stimulant action of capsaicin on peristalsis is independent of tachykinins acting via NK1 or NK2 receptors, while the delayed capsaicin-induced depression of peristalsis involves CGRP and NO.
DOI：
10.1152/ajpgi.1990.259.5.g889
发表时间：
1990-11
期刊：
The American journal of physiology
影响因子：
--
作者：
E. Mayer;C. Koelbel;W. Snape;V. Eysselein;H. Ennes;A. Kodner
通讯作者：
E. Mayer;C. Koelbel;W. Snape;V. Eysselein;H. Ennes;A. Kodner