使用选择性拮抗剂来分离速激肽对大鼠NK1和NK2受体的中枢心血管和行为效应。

Use of selective antagonists to dissociate the central cardiovascular and behavioural effects of tachykinins on NK1 and NK2 receptors in the rat.

Tschöpe C, Picard P, Culman J, Prat A, Itoi K, Regoli D, Unger T, Couture R

Department of Pharmacology, University of Heidelberg, Germany.

Br J Pharmacol. 1992 Nov;107(3):750-5. doi: 10.1111/j.1476-5381.1992.tb14518.x.

Abstract

The effects of intracerebroventricular (i.c.v.) pretreatment with selective NK1 ((+/-)-CP 96,345), NK2a (MEN 10,207; MEN 10,376) and NK2b (R 396) tachykinin receptor antagonists on the cardiovascular and behavioural responses to i.c.v. substance P (SP) and neurokinin A (NKA) were studied in conscious rats. 2. SP and NKA (25 pmol) induced mean arterial blood pressure and heart rate increases of the same magnitude and duration. The cardiovascular responses to both peptides were accompanied by excessive face washing, sniffing, grooming and wet dog shakes. 3. The cardiovascular responses to SP but not to NKA were attenuated by pretreatment with a NK1 receptor antagonist, (+/-)-CP 96,345. Of the behavioural responses, only face washing was significantly inhibited. 4. The cardiovascular and behavioural effects of NKA but not of SP were significantly attenuated by pretreatment with the selective NK2b receptor antagonist, R 396. 5. The selective NK2a receptor antagonists, MEN 10,207 and MEN 10,376, did not affect the cardiovascular and behavioural responses to either SP or NKA. 6. These results suggest, firstly, that the cardiovascular and behavioural effects of i.c.v. SP are mediated by NK1 receptors; secondly, that NKA injected i.c.v. does not interact with NK1 receptors but with another type of tachykinin receptor which may belong to the NK2b subclass. These findings provide pharmacological evidence for the existence of functionally active NK2 receptors in the rat brain.

摘要

在清醒大鼠中，研究了经脑室注射（i.c.v.）选择性NK1（(+/-)-CP 96,345）、NK2a（MEN 10,207；MEN 10,376）和NK2b（R 396）速激肽受体拮抗剂预处理后，对i.c.v.注射P物质（SP）和神经激肽A（NKA）的心血管及行为反应的影响。2. SP和NKA（25 pmol）引起平均动脉血压和心率升高，幅度和持续时间相同。对这两种肽的心血管反应均伴有过度洗脸、嗅探、梳理毛发和湿狗样抖动。3. 用NK1受体拮抗剂(+/-)-CP 96,345预处理可减弱对SP的心血管反应，但对NKA无此作用。在行为反应中，只有洗脸受到显著抑制。4. 用选择性NK2b受体拮抗剂R 396预处理可显著减弱NKA的心血管和行为效应，但对SP无此作用。5. 选择性NK2a受体拮抗剂MEN 10,207和MEN 10,376对SP或NKA的心血管和行为反应均无影响。6. 这些结果表明，首先，i.c.v.注射SP的心血管和行为效应由NK1受体介导；其次，i.c.v.注射的NKA不与NK1受体相互作用，而是与另一种可能属于NK2b亚类的速激肽受体相互作用。这些发现为大鼠脑中存在功能活跃的NK2受体提供了药理学证据。