ABSTRACT
Cholecystokinin, produced in the proximal small intestine, is a short acting satiating peptide hormone. CCK-10, before and after mono-iodination, was previously coupled to 10kDa polyethylene glycol (PEG). The formed conjugates PEG10kDa-CCK-10 and PEG10kDa-[(127)I]-CCK-10 show after i.p. administration to rats a sustained food intake reduction during 8h in comparison to 2h for free CCK-10. The present study examined the blood pharmacokinetics of this pharmacological interesting molecule by means of PEG10kDa-[(123)I]-CCK-10 following intravenous, intraperitoneal, intramuscular and nasal administration and the biodistribution after i.p. administration. HPLC analysis with radiometric detection allowed the differentiation between inorganic iodide and the intact tracer in blood. Blood kinetics after i.v. injection was fitted to a bi-exponential with a distribution half-life of 15 min and with an elimination half-life of 8 hours for intact PEG10kDa-[(123)I]-CCK-10. The biodistribution studies showed a higher accumulation of the tracer for all administration routes in organs expressing CCK receptors localized in the gastrointestinal tract such as pancreas, duodenum and small intestine. No indication of blood brain barrier crossing for the conjugate could be observed independently of the administration route. Main clearance was via the urinary pathway.
Subject(s)
Cholecystokinin/blood , Drug Carriers/pharmacokinetics , Iodine Radioisotopes/blood , Peptide Fragments/blood , Polyethylene Glycols/pharmacokinetics , Animals , Cholecystokinin/administration & dosage , Cholecystokinin/urine , Drug Administration Routes , Drug Carriers/administration & dosage , Drug Carriers/chemical synthesis , Drug Carriers/chemistry , Half-Life , Iodine Radioisotopes/urine , Male , Peptide Fragments/administration & dosage , Peptide Fragments/urine , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/chemistry , Rats , Rats, Wistar , Tissue DistributionABSTRACT
Concentration of Cholecystokinin(CCK) and Somatostantin(SS) in Plasma, 24 h urine and morning urine were observed in 57 pilots (22-45 years, mean 27.9) and 60 ground crew (23-47 years, mean 30.7). The results showed that CCK level in plasma, 24 h urine and morning urine (20.14 +/- 4.15, 10.08 +/- 2.29 and 11.29 +/- 2.18 pmol/L respectively) in pilots were significantly lower than those in ground crew (22.89 +/- 3.76, 7.04 +/- 1.03, 8.10 +/- 1.94 pmol/ L respectively) and those of SS were distinctly higher than in ground crew (12.38 +/- 2.34, 6.75 +/- 1.18, 7.41 +/- 1.27pmol/L respectively). Concentration of CCK and SS in plasma were positively related to those in 24 h urine and morning urine both in pilots and ground crew. It suggests that these changes might play potential role in the pathogenesis of some diseases of digestive system in pilots.
Subject(s)
Aerospace Medicine , Cholecystokinin/metabolism , Somatostatin/metabolism , Adult , China , Cholecystokinin/blood , Cholecystokinin/urine , Gastrointestinal Diseases/etiology , Humans , Middle Aged , Military Personnel , Somatostatin/blood , Somatostatin/urineSubject(s)
Cholecystokinin/urine , Immunoassay/methods , Animals , Buffers , False Positive Reactions , Humans , Rabbits , Serum Albumin, BovineABSTRACT
In patients with chronic pancreatitis (CP) (cholepancreatitis and primary recurrent pancreatitis), a moderate decrease of urocholecystokinin (UCK) excretion as a criterion for incretion of cholecystokinin-pancreozymin (CK) by duodenal endocrine cells was recorded in the presence of concomitant atrophic duodenitis. The beta-adrenoblocker obsidan, the blocker of m-cholinergic receptors gastrozepin, the antagonist of calcium channels finoptin and the synthetic analog of endogenous opiates dalargin reduced excretion of UCK in CP exacerbation. The decrease of CK incretion can be viewed as one of the mechanisms of the therapeutic action of these drugs in CP exacerbations. In the stage of CP remission, calcium gluconate consistently increased basal and intraduodenal oil (as a realizer of CK incretion) infusion-stimulated excretion of UCK. The enhancement of duodenal incretory activity is an essential mediating mechanism by which calcium gluconate stimulates pancreatic enzyme excretion.
Subject(s)
Cholecystokinin/metabolism , Pancreatitis/physiopathology , Animals , Biological Assay , Cholecystokinin/drug effects , Cholecystokinin/urine , Chronic Disease , Duodenum/drug effects , Duodenum/metabolism , Gallbladder/drug effects , Guinea Pigs , Humans , Pancreatitis/drug therapy , Pancreatitis/urine , RecurrenceABSTRACT
To diagnose biliary dyskinesia (BD) in children, a method of urine alpha-amylase measurement is offered. It is based on the presence of a direct and close correlation between amylase activity and the amount of endogenous cholecystokinin-pancreozymin in the same portion of the urine. It is concluded that fractional measurement of urine alpha-amylase can be used for diagnosing BD in childhood as a tentative test. It is advisable that it may be used for examining younger children and in cases where the employment of other methods of examination is not feasible.
