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

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.