Interaction of cholecystokinin (CCK-33) and its C-terminal fragments: CCK-8 and CCK-4 with alpha- and beta-adrenoceptor agonists and antagonists in the cardiovascular system of diabetic rats. Part B.

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.