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. 1998

R J Wiśniewska
Department of Pharmacology, Medical University, Białystok, Poland.

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.

UI MeSH Term Description Entries
D007545 Isoproterenol Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. Isoprenaline,Isopropylarterenol,4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol,Euspiran,Isadrin,Isadrine,Isopropyl Noradrenaline,Isopropylnoradrenaline,Isopropylnorepinephrine,Isoproterenol Hydrochloride,Isoproterenol Sulfate,Isuprel,Izadrin,Norisodrine,Novodrin,Hydrochloride, Isoproterenol,Noradrenaline, Isopropyl,Sulfate, Isoproterenol
D008297 Male Males
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D010646 Phentolamine A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of RAYNAUD DISEASE and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease. Fentolamin,Phentolamine Mesilate,Phentolamine Mesylate,Phentolamine Methanesulfonate,Phentolamine Mono-hydrochloride,Regitine,Regityn,Rogitine,Z-Max,Mesilate, Phentolamine,Mesylate, Phentolamine,Methanesulfonate, Phentolamine,Mono-hydrochloride, Phentolamine,Phentolamine Mono hydrochloride
D011433 Propranolol A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs. Dexpropranolol,AY-20694,Anaprilin,Anapriline,Avlocardyl,Betadren,Dociton,Inderal,Obsidan,Obzidan,Propanolol,Propranolol Hydrochloride,Rexigen,AY 20694,AY20694,Hydrochloride, Propranolol
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D002319 Cardiovascular System The HEART and the BLOOD VESSELS by which BLOOD is pumped and circulated through the body. Circulatory System,Cardiovascular Systems,Circulatory Systems
D002766 Cholecystokinin A peptide, of about 33 amino acids, secreted by the upper INTESTINAL MUCOSA and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. Pancreozymin,CCK-33,Cholecystokinin 33,Uropancreozymin
D003921 Diabetes Mellitus, Experimental Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY. Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal

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