Culman J, Tschöpe C, Jost N, Itoi K, Unger T
Department of Pharmacology, University of Heidelberg, Germany.
Brain Res. 1993 Oct 15;625(1):75-83. doi: 10.1016/0006-8993(93)90139-e.
Desensitization and cross-desensitization to the cardiovascular and behavioral effects elicited by intracerebroventricular (i.c.v.) substance P (SP) and neurokinin A (NKA) injections were examined in conscious, freely moving rats. The cardiovascular responses to equimolar doses of both peptides were identical, however, the pattern of the behavioral responses differed. Relative to SP, NKA was weaker in eliciting hindquarter grooming but more effective in eliciting wet dog shakes. SP pretreatment (50 pmol) desensitized the cardiovascular and behavioral responses to both, subsequent injections of SP (50 pmol) as well as of NKA (50 or 500 pmol) injected 30 or 60 min after SP, indicating cross-desensitization. NKA pretreatment (50 pmol) partly reduced the cardiovascular but not the behavioral responses to subsequent equimolar doses of NKA. The cardiovascular responses to SP (50 pmol) were reduced only 30 min but not 60 min after pretreatment with a 10 times higher dose of NKA (500 pmol). Of all behavioral manifestations to i.c.v. SP, only hindquarter grooming was attenuated by pretreatment with either dose of NKA. The equal potency of SP and NKA in eliciting the cardiovascular effects but different pattern of behavioral responses to these peptides suggest an involvement of different types of tachykinin receptors in mediating the central effects of the two peptides. The fact that NKA induced cross-desensitization selectively to one type of behavioral manifestations elicited by SP, indicates the existence of two subtypes of SP (NK1) receptors in the rat brain.
在清醒、自由活动的大鼠中，研究了对脑室内（i.c.v.）注射P物质（SP）和神经激肽A（NKA）所引发的心血管和行为效应的脱敏和交叉脱敏情况。两种肽等摩尔剂量引发的心血管反应相同，然而，行为反应模式不同。相对于SP，NKA引发后肢梳理的能力较弱，但引发湿狗样抖动的效果更明显。SP预处理（50 pmol）使对随后注射的SP（50 pmol）以及在SP注射后30或60分钟注射的NKA（50或500 pmol）的心血管和行为反应脱敏，表明存在交叉脱敏。NKA预处理（50 pmol）部分降低了对随后等摩尔剂量NKA的心血管反应，但未降低行为反应。用高10倍剂量的NKA（500 pmol）预处理后，对SP（50 pmol）的心血管反应仅在30分钟后降低，60分钟后未降低。在对i.c.v. SP的所有行为表现中，只有后肢梳理会因任何一种剂量的NKA预处理而减弱。SP和NKA在引发心血管效应方面具有同等效力，但对这些肽的行为反应模式不同，这表明不同类型的速激肽受体参与介导这两种肽的中枢效应。NKA选择性地诱导对SP引发的一种行为表现的交叉脱敏，这一事实表明大鼠脑中存在两种SP（NK1）受体亚型。
