Fading and tachyphylaxis to the contractile effects of substance P in the guinea-pig ileum.
Fading and tachyphylaxis to the contractile effects of substance P in the guinea-pig ileum.
复制标题
P 物质在豚鼠回肠中的收缩作用的褪色和快速耐受。
DOI：
10.1016/0014-2999(82)90597-0
复制
发表时间：
1982
影响因子：
5
通讯作者：
Musacchio,JM
中科院分区：
文献类型：
--
作者：
Huidobro-Toro,JP;Chelala,CA;Bahouth,S;Nodar,R;Musacchio,JM
P物质（SP）引起豚鼠回肠纵行平滑肌层立即剧烈收缩。与乙酰胆碱或组胺不同，SP的收缩反应没有维持，但在约6分钟内消退到基线水平。当加入0.3-1.0 nM SP时，消退时间短于6分钟，快速耐受没有发展。较高浓度的SP产生约6分钟的褪色时间，即使加入极高浓度的肽，高达1 800 nM，也不能增加。短褪色时间和缺乏快速耐受的发展是由于快速吸附和/或代谢的SP。添加外源肽酶，如链霉蛋白酶，糜蛋白酶和提取物的黑寡妇蜘蛛毒腺显着增加SP的降解率，缩短褪色反应和阻断快速耐受的发展。河豚毒素和阿托品减少了褪色时间的25%，而Esplatin增加其持续时间的几倍，这些研究结果是一致的存在的胆碱能神经成分在调解的一些影响SP。这些研究demonstrate，褪色的收缩作用的SP是一个复杂的现象，由于脱敏的SP受体，并在一定程度上，吸附和代谢的肽。SP的快速耐受的幅度与肽的脱敏剂量的浓度成正比，并且对SP和相关肽毒蜥毒蛋白是特异性的;没有发现对其他药剂的交叉快速耐受。
Substance P (SP) caused an immediate and vigorous contraction of the longitudinal smooth muscle layer of the guinea-pig ileum. The contractile response to SP, unlike that to acetylcholine or histamine was not maintained but faded to baseline levels in about 6 min. When 0.3–1.0 nM SP was added the fading time was shorter than 6 min and tachyphylaxis did not develop. Higher concentrations of SP produced fading times of about 6 min that could not be increased even by adding extremely high concentrations of the peptide, up to 1 800 nM. Short fading timesand the lack of development of tachyphylaxis are the resulst of the rapid adsorption and/or metabolism of SP. The addition of exogenous peptidases such as pronase, chymotrypsin and an extract of black widow spider venom gland dramatically increased the rate of degradation of SP, shortened the fading response and blocked the development of tachyphylaxis. Tetrodotoxin and atropine reduced the fading time by 25%, while eserine increased its duration several-fold; these findings are consistent with the existence of a cholinergic nerve component in the mediation of some of the effects of SP. These studies demontrate that fading of the contractile effects of SP is a complex phenomenon due to desensitization of the SP receptor and, in part, to adsorption and metabolism of the peptide. The magnitude of the tachyphylaxis to SP was proportional to the concentration of the desensitizing dose of the peptide and was specific to SP and to the related peptide physalaemin; no cross-tachyphylaxis towards other agents was found.