MECHANISM OF ACTION OF SUBSTANCE-P IN GUINEA-PIG ILEUM LONGITUDINAL SMOOTH-MUSCLE - A REEVALUATION
MECHANISM OF ACTION OF SUBSTANCE-P IN GUINEA-PIG ILEUM LONGITUDINAL SMOOTH-MUSCLE - A REEVALUATION
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DOI：
10.1113/jphysiol.1990.sp018345
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发表时间：
1990-12-01
影响因子：
5.5
通讯作者：
MORTON, IKM
中科院分区：
文献类型：
--
作者：
HALL, JM;MORTON, IKM
本文对P物质收缩豚鼠回肠纵行肌膜K+通透性(PK)的机制进行了重新探讨。K+通道阻滞剂四乙基铵(TEA)增强P物质的反应最初被认为是P物质降低PK的作用机制的证据。增强作用得到了证实；然而，这并不是P物质所特有的，因为类似的反应增强与激动剂并不被认为是通过降低pk起作用的。去甲肾上腺素对P物质的收缩反应的拮抗作用也同样得到证实。然而，这种拮抗作用被发现是通过β-肾上腺素受体的抑制作用而不是所提出的与去甲肾上腺素增加PK的特定相互作用而表现出的非特异性功能相互作用，去甲肾上腺素通常是由α1-肾上腺素受体介导的。实验测定去极化豚鼠回肠纵行肌条86Rb流出量，以估算PK。这些研究证实了用TEA降低PK的报道，但未能检测到先前报道的P物质的降低。这些结果虽然没有反驳P物质直接收缩豚鼠回肠纵肌的机制，但确实对原作者支持这种机制的证据或其解释提出了质疑。
A proposed mechanism of contractile action of substance P in guinea-pig ileum longitudinal smooth muscle involving a decrease in membrane K+ permeability (PK) has been re-examined. Potentiation of responses to substance P by the K+ channel blocker tetraethylammonium (TEA) was originally proposed as evidence for a mechanism of action of substance P involving a decrease in PK. Potentiation was confirmed; however this was found not to be specific to substance P since a similar potentiation of responses was seen with agonists not thought to act via a decrease in PK. Antagonism of contractile responses to substance P by noradrenaline was similarly confirmed. However, this antagonism was found to represent a non-specific functional interaction through the inhibitory actions of .beta.-adrenoceptors rather than the proposed specific interaction with an increase in PK by noradrenaline which is normally .alpha.1-adrenoceptor mediated. Experiments were made measuring 86Rb efflux, in depolarized guinea-pig ileum longitudinal smooth muscle, to estimate PK. These studies confirmed a reported decrease in PK with TEA, but failed to detect the previously reported decrease with substance P. These results, although not disproving a suggested mechanism of direct contractile action of substance P in guinea-pig ileum longitudinal smooth muscle involving a decrease in PK, do throw doubt on either the evidence, or its interpretation, as proposed by the original authors in support of such a mechanism.