Wiśniewska R J
Department of Pharmacology, Medical University, Białystok, Poland.
Pol J Pharmacol. 1998 May-Jun;50(3):213-23.
This study investigated the interaction of cholecystokinin (CCK-33) and its fragments: C-terminal octapeptide (CCK-8) and C-terminal tetrapeptide (CCK-4) with alpha- and beta-adrenoceptor agonists and antagonists. The effects of this interaction on arterial blood pressure and function of isolated heart were studied in rats with 1-month diabetes mellitus (DM) induced by 1-month administration of streptozocin (STZ). We used CCK-33, CCK-8 and CCK-4 in an equimolar dose of 425.0 pmoles/kg i.v. in in vivo, and 42.5 pmoles/0.1 ml in in vitro experiments. We found that 1) DM diminished the hypertensive effect of noradrenaline (NA) and the hypotensive effects of isoprenaline (ISO), phentolamine (PHENT) and propranolol (PROP). CCK-4 and CCK-8 enhanced but CCK-33 did not change a weaker hypertensive effect of NA while all peptides showed the hypotensive effect of PHENT and did not change the hypotensive effect of ISO and PROP. 2) The influence of NA and PROP on isolated heart of diabetic rats remained unchanged after administration of the peptides but that of ISO and PHENT was diminished. CCK-4 enhanced the effects of NA and PHENT, and diminished the influence of ISO and PROP on isolated heart of diabetic rats. CCK-33 enhanced the cardiac effects of NA, ISO and PROP and did not alter PHENT action. CCK-8 did not change the influence of the studied adrenoceptor agonists and antagonists on isolated heart of diabetic rats. The results of the present study demonstrated that the smallest fragment of CCK-33 (CCK-4) modified the influence of alpha- and beta-adrenoceptor agonists and antagonists on cardiovascular system and altered the direction of disturbances caused by DM. The other peptides (CCK-33, CCK-8) interacted with these receptors to a lesser degree in diabetic subjects.
本研究调查了胆囊收缩素（CCK - 33）及其片段：C末端八肽（CCK - 8）和C末端四肽（CCK - 4）与α和β肾上腺素能受体激动剂及拮抗剂之间的相互作用。在通过给予链脲佐菌素（STZ）诱导1个月糖尿病（DM）的大鼠中，研究了这种相互作用对动脉血压和离体心脏功能的影响。我们在体内实验中以425.0皮摩尔/千克静脉注射的等摩尔剂量使用CCK - 33、CCK - 8和CCK - 4，在体外实验中以42.5皮摩尔/0.1毫升的剂量使用。我们发现：1）糖尿病减弱了去甲肾上腺素（NA）的升压作用以及异丙肾上腺素（ISO）、酚妥拉明（PHENT）和普萘洛尔（PROP）的降压作用。CCK - 4和CCK - 8增强了NA较弱的升压作用，但CCK - 33未改变；而所有肽均显示出PHENT的降压作用，且未改变ISO和PROP的降压作用。2）给予肽后，NA和PROP对糖尿病大鼠离体心脏的影响保持不变，但ISO和PHENT的影响减弱。CCK - 4增强了NA和PHENT的作用，并减弱了ISO和PROP对糖尿病大鼠离体心脏的影响。CCK - 33增强了NA、ISO和PROP的心脏效应，且未改变PHENT作用。CCK - 8未改变所研究的肾上腺素能受体激动剂和拮抗剂对糖尿病大鼠离体心脏的影响。本研究结果表明，CCK - 33的最小片段（CCK - 4）改变了α和β肾上腺素能受体激动剂及拮抗剂对心血管系统的影响，并改变了由糖尿病引起的紊乱方向。其他肽（CCK - 33、CCK - 8）在糖尿病患者中与这些受体的相互作用程度较小。
