摘要
过去的工作已经证明八肽胆囊收缩素(CCK-8)能够对抗阿片肽的镇痛作用,本工作探讨CCK-8是否能够对抗阿片肽的心血管抑制作用。给戊巴比妥钠麻醉大鼠脊髓蛛网膜下腔(ith)注射 CCK-8可以对抗 ith 注射 mu(μ)型阿片受体激动剂[NMePhe^3,D-Pro^4]Morphiceptin(PL017)(5μg)、delta(δ)型受体激动剂[D-Ala^2,D-Leu^5]Enkephalin(DADLE)(25μg)和 Kappa(K)型受体激动剂[N-Me Tyr,N-Me Arg^7,D-Leu^8]Dynorphin 1-8 ethyla-mide(66A-078)(1μg)引起的降低血压和减慢心率作用。在 MAP 的表现上,CCK-8的拮抗作用(10μg及以下剂量)具有量-效关系,并可被 CCK 受体阻断剂丙谷胺(Proglumide)(100μg)翻转。在 HR 的表现上,上述剂量的 CCK-8也显示了一定的拮抗作用,但量-效关系不如 MAP 表现得明显。单纯将 CCK-8或 Proglumide ith 注射,可见大剂量(50μg)CCK-8可以引起明显的降血压作用和短时的降心率作用,小剂量(0.05μg)CCK-8则表现出明显的降心率作用;ith 注射 Proglumide 100μg,30 min 后也表现出减慢心率的作用。以上结果提示:在脊髓水平,一定剂量范围内的 CCK-8能够对抗阿片肽的心血管抑制效应,此对抗作用是通过 CCK 受体实现的。本工作的结果支持关于 CCK-8是一种抗阿片物质的设想。
Cholecystokinin-octapeptide(CCK-8)has been shown to antagonize the an-algesia produced by opioid peptides.The present study was performed to evaluateits effect on cardiovascular regulatory functions of opioids.Both CCK-8 and opioidpeptides were injected intrathecally(ith)in pentobarbital anaesthetized rats.Thedepressive effects induced by the mu agonist PL017(5 μg)delta agonist DADLE(25 μg)and kappa agonist 66A-078(1 μg)were antagonized by CCK-8 within adosage of 10μg in a dose dependent manner.CCK-8 can also partly antagonizethe bradycardiac effects induced by PL017,DADLE and 66A-078.The antagonistic effect of CCK-8 on DADLE in MAP could be reversed bypretreatment with CCK receptor antagonist proglumide(100μg).No significantchanges in MAP were found following ith administration of CCK-8 0.5-10μgand proglumide 100 μg,but a large dose(50μg)of CCK-8 lowered MAP dra-matically.The results suggest that within a certain range of dose CCK-8 in spinal cordmay play an antagonistic role against opioid effects in the regulation of cardio-vascular function and this effect of CCK-8 seems to be mediated by CCK recep-tor.These results support the hypothesis that CCK-8 may act as an anti-opioidsubstance in the CNS of the rat.
出处
《生理学报》
CAS
CSCD
北大核心
1991年第2期156-163,共8页
Acta Physiologica Sinica
关键词
CCK-8
阿片肽
降压作用
cholecystokinin-octapeptide
opioid peptide
intrathecal injection
meanarterial pressure
heart rate
