Holzer P, Schluet W, Maggi C A
University Department of Experimental and Clinical Pharmacology, Graz, Austria.
J Pharmacol Exp Ther. 1995 Jul;274(1):322-8.
The tachykinins substance P (SP) and neurokinin A participate in the neural control of intestinal peristalsis. This study aimed at elucidating the types of tachykinin receptors involved in SP's ability first to stimulate and then to inhibit propulsive activity. Peristalsis in the guinea pig isolated ileum was triggered by fluid-induced distension of the intestinal wall. Unlike SP, the neurokinin (NK)-1 receptor-selective agonist SP methyl ester (1-100 nM) failed to facilitate peristalsis but caused a delayed inhibition of peristaltic activity. In contrast, the NK-2 receptor-selective agonist [beta-Ala8]-NKA-(4-10) (BANKA, 1-100 nM) stimulated, but did not inhibit, peristalsis. The NK-3 receptor-selective agonist succinyl-[Asp6,N-MePhe8]-substance P-(6-11) (SENKTIDE, 0.1-10 nM) was most potent in facilitating propulsive activity, and only with 10 nM SENKTIDE was a delayed inhibition of peristalsis seen. The receptors responsible for the tachykinin-evoked stimulation and inhibition of peristaltic activity were further characterized by use of the NK-1 receptor-selective antagonist (+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994, 300 nM) and the NK-2 selective antagonist (-)-N-methyl-N[4-acetylamino-4-phenyl-piperidino-2 (3,4 dichlorophenyl)butyl]-benzamide (SR-48,968, 100 nM). CP-99,994 antagonized the inhibitory effects of SP (100 nM) and SP methyl ester (100 nM) on peristalsis but did not alter the facilitation of propulsive motility brought about by SP or BANKA (100 nM). Conversely, SR-48,968 (100 nM) suppressed the ability of SP and BANKA to stimulate persitaltic activity but did not attenuate the inhibitory motor effects of SP and SP methyl ester.(ABSTRACT TRUNCATED AT 250 WORDS)
速激肽P物质（SP）和神经激肽A参与肠道蠕动的神经控制。本研究旨在阐明参与SP先刺激然后抑制推进活动能力的速激肽受体类型。豚鼠离体回肠中的蠕动由液体诱导的肠壁扩张引发。与SP不同，神经激肽（NK）-1受体选择性激动剂SP甲酯（1 - 100 nM）未能促进蠕动，但导致蠕动活动延迟抑制。相反，NK - 2受体选择性激动剂[β - Ala8]-NKA -（4 - 10）（BANKA，1 - 100 nM）刺激但不抑制蠕动。NK - 3受体选择性激动剂琥珀酰 - [Asp6，N - MePhe8]-P物质 -（6 - 11）（SENKTIDE，0.1 - 10 nM）在促进推进活动方面最有效，仅在10 nM SENKTIDE时可见蠕动的延迟抑制。通过使用NK - 1受体选择性拮抗剂（+） - （2S，3S） - 3 - （2 - 甲氧基苄基氨基） - 2 - 苯基哌啶（CP - 99,994，300 nM）和NK - 2选择性拮抗剂（ - ） - N - 甲基 - N[4 - 乙酰氨基 - 4 - 苯基 - 哌啶基 - 2（3,4 - 二氯苯基）丁基] - 苯甲酰胺（SR - 48,968，100 nM）进一步表征了负责速激肽诱发的蠕动活动刺激和抑制的受体。CP - 99,994拮抗SP（100 nM）和SP甲酯（100 nM）对蠕动的抑制作用，但不改变SP或BANKA（100 nM）引起的推进运动促进作用。相反，SR - 48,968（100 nM）抑制SP和BANKA刺激蠕动活动的能力，但不减弱SP和SP甲酯的抑制性运动效应。（摘要截短于250字）
