Central cardiovascular and behavioral effects of carboxy- and amino-terminal fragments of substance P in conscious rats

Abstract

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 NK 1 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 NK 1 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 NK 1 receptor like SP 1–11.