Tschöpe C, Jost N, Unger T, Culman J
Department of Pharmacology, Christian-Albrechts University of Kiel, Germany.
Brain Res. 1995 Aug 28;690(1):15-24. doi: 10.1016/0006-8993(95)00577-d.
The central cardiovascular and behavioral effects of carboxy- (SP 5-11, SP 6-11, SP 7-11, SP 8-11) and amino- (SP 1-7, SP 1-9) terminal substance P (SP) fragments were compared with those of SP 1-11 in conscious rats. In addition, the ability of these SP-fragments to induce desensitization of the central NK1 receptor was investigated. SP 1-11 (50 pmol) injected i.c.v. induced an increase in mean arterial blood pressure (MAP), heart rate (HR) and a typical behavioral response consisting of face washing (FW), hindquarter grooming (HQG) and wet-dog shakes (WDS). The cardiovascular and behavioral responses to equimolar doses of SP 5-11 and SP 6-11 were similar to those of SP 1-11, however, only SP 5-11 induced exactly the same behavioral pattern as SP 1-11. SP 6-11 was more potent in inducing FW and WDS than SP 1-11 or SP 5-11. The carboxy-terminal SP-fragments, SP 7-11 and SP 8-11, and the amino-terminal SP-fragments, SP 1-7, SP 1-9, did not elicit any significant cardiovascular or behavioral responses. Pretreatment with SP 1-11 reduced the cardiovascular and behavioral responses to subsequent injections of SP 1-11. Of all SP-fragments tested, only SP 5-11 was able to attenuate the cardiovascular and behavioral responses to SP 1-11. Our results demonstrate that SP 6-11 represents the shortest carboxy-terminal amino acid sequence, that after i.c.v. injection, elicits the same cardiovascular response as SP 1-11, but fails to desensitize the NK1 receptor. The carboxy-terminal fragment, SP 5-11, is the shortest amino acid sequence which produces the same pattern of central cardiovascular and behavioral responses as SP 1-11 and also retains the ability to desensitize the NK1 receptor like SP 1-11.
在清醒大鼠中，比较了羧基末端（SP 5 - 11、SP 6 - 11、SP 7 - 11、SP 8 - 11）和氨基末端（SP 1 - 7、SP 1 - 9）P物质（SP）片段与SP 1 - 11对心血管和行为的中枢效应。此外，还研究了这些SP片段诱导中枢NK1受体脱敏的能力。脑室内注射50 pmol的SP 1 - 11可使平均动脉血压（MAP）、心率（HR）升高，并引发典型的行为反应，包括洗脸（FW）、后肢梳理（HQG）和湿狗抖身（WDS）。等摩尔剂量的SP 5 - 11和SP 6 - 11引起的心血管和行为反应与SP 1 - 11相似，然而，只有SP 5 - 11引发的行为模式与SP 1 - 11完全相同。SP 6 - 11在诱导FW和WDS方面比SP 1 - 11或SP 5 - 11更有效。羧基末端SP片段SP 7 - 11和SP 8 - 11以及氨基末端SP片段SP 1 - 7、SP 1 - 9未引发任何显著的心血管或行为反应。用SP 1 - 11预处理可降低对后续注射SP 1 - 11的心血管和行为反应。在所有测试的SP片段中，只有SP 5 - 11能够减弱对SP 1 - 11的心血管和行为反应。我们的结果表明，SP 6 - 11代表最短的羧基末端氨基酸序列，脑室内注射后，引发与SP 1 - 11相同的心血管反应，但不能使NK1受体脱敏。羧基末端片段SP 5 - 11是最短的氨基酸序列，它产生与SP 1 - 11相同的中枢心血管和行为反应模式，并且还保留了像SP 1 - 11一样使NK1受体脱敏的能力。
