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PubMed1994

In man the mu-opiate agonist loperamide specifically inhibits ACTH secretion induced by the cholecystokinin-like peptide ceruletide.

Ceruletide, a cholecystokinin-8-like peptide, was recently reported to stimulate ACTH secretion in man. The aim of this study was to investigate the effect of the mu-opiate agonist, loperamide, and the opiate antagonist, naloxone, on ceruletide-induced ACTH secretion in man. In 6 normal subjects, basal ACTH and cortisol plasma levels were significantly suppressed 3 h after loperamide administration (16 mg, orally) from 5 +/- 0 to 2 +/- 0 pmol/l and from 356 +/- 44 to 154 +/- 16 nmol/l. After stimulation with 8 ng ceruletide/kg body weight/min over a period of 5 min, the maximum ACTH levels (at 7.5 min) were significantly reduced by loperamide from 26 +/- 7 to 6 +/- 1 pmol/l and the maximum cortisol levels (at 30 min) were significantly reduced from 676 +/- 47 to 392 +/- 58 nmol/l. Furthermore, the ACTH peak (delta = 7.5 min) was significantly blunted by loperamide from 21 +/- 7 to 5 +/- 1 pmol/l and the integrated area under the curve from 0 to 120 min (delta AUC) of ACTH was significantly reduced from 40 +/- 11 to 14 +/- 4 pmol x 120 min/l. The cortisol peak (delta = 30 min) and the AUC of cortisol were not significantly diminished. The suppressive effect of loperamide on basal and ceruletide-induced ACTH and cortisol secretion was completely reversed by the administration of 0.8 mg naloxone, 20 min before and during infusion of ceruletide. The administration of naloxone itself had no significant effect on ACTH or cortisol levels. In conclusion, ACTH is released by peripherally administered ceruletide within a short period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1995

Influence of ceruletid on gallbladder contraction: a possible prophylaxis of acute acalculous cholecystitis in intensive care patients?

The purpose of this study was to investigate the utility of repeated applications of ceruletid to reduce gallbladder volume and its feasibility as a means of prophylaxis of acute acalculous cholecystitis in intensive care patients. First, a dose-response curve of ceruletid was obtained in 20 mechanically ventilated patients of a surgical intensive care unit (SICU) not receiving enteral nutrition. An effective dose of ceruletid, defined by a 50% reduction of gallbladder volume was established and subsequently studied in 40 mechanically ventilated SICU patients on total parenteral nutrition in a prospective, randomized, controlled, triple-blind trial. Gallbladder volume, sludge formation and side effects were evaluated. A dose of 1.5 micrograms/kg body weight ceruletid was established as the effective dose, causing 50% reduction of gallbladder volume in all patients studied and reduction of gallbladder sludge in 95%. In 67.5% of patients side effects were observed, requiring therapeutic intervention in 68%. It is concluded that ceruletid is effective in stimulating gallbladder contraction and reducing sludge formation in severely ill patients on intensive care units. Its routine use as prophylaxis of acute acalculous cholecystitis, however, may be limited by the nature, severity and frequency of side effects.

Acute Disease↗
PubMed2000

Serum feline trypsin-like immunoreactivity following administration of ceruletide to healthy cats.

OBJECTIVE: To determine changes in serum feline trypsin-like immunoreactivity (fTLI) in response to administration of ceruletide to healthy cats. ANIMALS: 11 healthy cats. PROCEDURES: Serum fTLI was determined, using a radioimmunoassay, before and 10, 20, 30, 40, and 50 minutes after IM administration of ceruletide (0.3 mg/kg [0.14 mg/lb]). RESULTS: Mean +/- SD baseline serum fTLI was 23.1 +/- 4.1 mg/L. There was a statistically significant, but clinically unimportant, increase in serum fTLI 10 and 30 minutes after ceruletide administration. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy cats, administration of ceruletide induced a statistically significant, but clinically unimportant, increase in serum fTLI. Whether responses in cats with exocrine pancreatic disorders would be different is unknown, but results suggest that a ceruletide stimulation test would likely not be useful for differentiating between healthy cats and cats with subclinical chronic exocrine pancreatic disorders.

Animals↗
PubMed1984

[Treatment of intestinal atony following gynecologic operations. Study on the effectiveness and tolerance of ceruletide].

The efficacy and tolerability of Ceruletide and Neostigmin were compared in patients with postoperative intestinal atonia after extensive gynecological surgical operations. Patients treated with Ceruletide (n = 30, dosage of Ceruletide 2 ng/kg/min. i.v.) showed earlier defecation than the Neostigmin-group (n = 30, dosage of neostigmin 3 x 0,5 mg/die). The frequency of side effects was comparable in both groups, patients treated with Ceruletide suffered mainly from gastrointestinal symptoms (nausea) whereas patients treated with Neostigmin complained of disorders of circulation. Ceruletide is faster effective than Neostigmin, the tolerability of both drugs is equivalent.

Blood Pressure↗
PubMed1984

The effects of ceruletide in schizophrenia.

Eight neuroleptic-resistant schizophrenic patients were treated with ceruletide diethylamine, a cholecystokininlike peptide, in a placebo-controlled, double-blind, cross-over study. Ceruletide or placebo was administered intramuscularly twice a day for four consecutive days while patients received a constant dose of fluphenazine hydrochloride. Cholecystokinin octapeptide was also administered to four different schizophrenic patients in a double-blind, cross-over study. Cholecystokinin or placebo was administered as a slow intravenous infusion daily for four days. There were no changes in either the positive or negative symptoms of schizophrenia between the periods of placebo, ceruletide, or cholecystokinin administration. Furthermore, there was no tendency for the patients' conditions to either improve or worsen during the course of ceruletide or cholecystokinin treatment. In contrast to previous reports from uncontrolled studies, cholecystokininlike peptides appear to be devoid of antipsychotic properties when administered parenterally.

Adult↗
PubMed1988

Non-invasive treatment for retained common bile duct stones in patients with T tube in situ: saline washout after intravenous ceruletide.

The combination of ceruletide-induced relaxation of the sphincter of Oddi plus flushing with saline has recently been proposed as a novel procedure for the treatment of residual common bile duct (CBD) stones. In this study we have administered intravenous ceruletide (2 ng kg-1 body weight min-1 for 1 h) plus intraductal saline (800-3000 ml, infused at a rate that kept biliary pressure below 30 cmH2O) to a group of 14 patients. The treatment induced the passage of residual stones in 11 subjects (79 per cent) with complete clearance in 7 (50 per cent). The majority of the cleared concretions (11/15) had a diameter less than 10 mm. No severe side-effects were recorded during the treatment. Four of the seven subjects who exhibited incomplete CBD clearance underwent a short cycle of mono-octanoin administration in order to reduce the size of residual radiolucent stones. This course of treatment was followed by another attempt with intravenous ceruletide and saline washout which gave a successful response in an additional three cases. These data indicate that the combination of ceruletide and flushing is a safe and inexpensive method for treatment of residual stones. The procedure is feasible for both radiolucent and radio-opaque stones and is mainly eligible for small concretions of diameter less than 10 mm. Larger (greater than 10 mm) radiolucent stones may be partially dissolved with mono-octanoin and then eliminated by the washout technique.

Adult↗
PubMedDate not supplied

Ultrasonic evaluation of gallbladder emptying with ceruletide: comparison to oral cholecystography with fatty meal.

Assessment of gallbladder function is required prior to nonsurgical treatment of gallstones. In order to develop a practical and reproducible method of evaluation, gallbladder emptying was studied by ultrasound (US) in 55 gallstone patients after intramuscular administration of ceruletide (0.3 micrograms/kg). In 27 of these subjects, the US procedure was compared to oral cholecystography (OCG) with fatty meal. Maximal percent gallbladder contraction was reached 30 min after ceruletide in all patients. Maximal percent contractions were 47.5 +/- 27.7 during US with ceruletide and 33.9 +/- 16.3 during OCG with fatty meal (p = 0.03). A significant linear relationship was found between the results obtained with the two different procedures (r = 0.57; p = 0.002). Serial US determinations of gallbladder emptying were performed in 16 patients. Individual variation was below 20% in 11 subjects, and in five subjects it ranged between 20 and 40%. Minor, self-limiting side effects were observed in 13 patients. US determination of gallbladder emptying after ceruletide appears to be a practical and reliable method to assess gallbladder function.

Adult↗
PubMed1986

Partial restoration of pancreatic function by exogenous secretin in rats with ceruletide-induced acute pancreatitis.

Pharmacological doses of ceruletide administered intravenously to unconscious rats uniformly induces acute pancreatitis (AP) as well as a striking reduction in pure pancreatic juice (PPJ) and protein output. High-dose intravenous secretin administered to rats with ceruletide-induced AP effects a reestablishment of PPJ flow and a significant increase in PPJ protein output. Light microscopy of the pancreas in ceruletide-induced AP rats revealed marked acinar cell vacuolization and intense interstitial edema. By contrast, pancreatic histology in AP rats treated with high-dose secretin revealed a distinct lessening of acinar cell vacuolization and interstitial edema. We have established that high-dose intravenous secretin given to rats with ceruletide-induced AP is (1) not harmful, (2) reestablishes PPJ flow and evokes a partial restoration of protein output, and (3) appears to reduce pancreatic histopathology when compared to non-secretin-treated rats with AP.

Acute Disease↗
PubMed1980

Acceleration of small intestine contrast study by ceruletide.

The effect of ceruletide on the small bowel transit time of barium sulfate suspension was studied in 165 patients. The control group consisted of 115 cases. An intramuscular injection of 500--750 ng/kg body weight ceruletide was given in 106 cases (group A), 20 ng/kg ceruletide was intravenously injected in 35 patients (group B), and 40 ng/kg was intravenously injected in 24 cases (group C). The mean transit time in group A was 62 +/- 41 min (mean +/- SD), and 126 +/- 62 min in the corresponding control group of 83 cases. (P less than 0.001). The mean transit time in group B was 65 +/- 50 min, and 69 +/- 56 min in group C, whereas in the corresponding control group of 32 cases the mean transit time was 137 +/- 79 min (P less than 0.01). A normal radiographic pattern was found in 75%, and slightly increased segmental contractions in 21%. Overtonicity and pronounced segmental contractions were seen in 4%. The recommended standardized small bowel study using ceruletide reduces the examination time by roughly one-half and produces simultaneous and uniform opacification of the jejunum and ileum.

Adult↗
PubMed1988

Bile duct measurements after ceruletide as an aid to the ultrasound diagnosis of choledocholithiasis.

Despite good results in gallbladder imaging, ultrasound (US) diagnosis of choledocholithiasis remains a challenge. The value of US before and after a provocative injection of the decapeptide ceruletide was examined in 25 patients with suspected common duct stones immediately prior to diagnostic retrograde cholangiography. An abnormal response (increase in US duct diameter) was seen in 4 of 6 patients with an obstructed duct, giving a sensitivity of 67% and predictive value of 80% for the procedure. There was a normal response (decrease in US diameter of a dilated duct or decrease/no change in a normal duct) in 14 of 19 with an unobstructed duct (specificity 79%, predictive value 93%) and an equivocal response (no change in diameter of a dilated duct) in 5 patients. In 1 patient a calculus not seen on the initial US became visible as the duct distended by ceruletide administration. Symptoms after ceruletide were few and not discriminatory. Although it added to the time and difficulty of performing biliary US, ceruletide administration proved a useful adjunct to the diagnosis of choledocholithiasis.

Bile Ducts↗
PubMed1985

Assessment of gallbladder function using ceruletide in oral cholecystography.

A dose of 0.3 micrograms/kg body weight of ceruletide was assessed for its effect on gallbladder contraction and bile duct delineation following oral cholecystography. Nausea, vomiting, and abdominal pain sometimes occurred after ceruletide. No relationship was found after ceruletide administration between the radiologic appearances of the biliary tract and reproduction of the patients' biliary-type symptoms. Ceruletide cholecystography is regarded as an inaccurate investigation of biliary tract function.

Adult↗
PubMed1986

Utility of ceruletide in promoting intestinal opacification for abdominal and pelvic computed tomography.

An analysis of the utility of parenteral ceruletide, a cholecystokinin-like synthetic decapeptide, in promoting bowel opacification for computed tomography (CT) scanning was performed. Abdominal and pelvic CT scans of 85 patients who had received intramuscular ceruletide following oral contrast administration and of 85 control patients were reviewed and the degree of bowel opacification evaluated. No significant advantage was conferred by ceruletide in opacifying the stomach or major part of the small intestine. However, a statistically significant difference was found between the 2 groups in the presence or absence of contrast in the terminal ileum and right colon. Contrast was detected in the terminal ileum in 52 experimental compared with 35 control patients (p less than 0.009) and in the right colon in 56 experimental and 39 control subjects (p less than 0.01). Intramuscular administration of ceruletide will be helpful when terminal ileal opacification is essential or in patients in whom colonic opacification is desired but rectal contrast contraindicated.

Ceruletide↗
PubMed1993

Effects of ceruletide on the dopamine receptor-adenylate cyclase system in striatum and frontal cortex of rats chronically treated with haloperidol.

Chronic treatment of rats with haloperidol decanoate (30 mg/kg and 100 mg/kg IM every 4 weeks for 52 weeks) increased [3H] SCH 23390 binding in striatal membranes by 25% and 50% and in frontal cortical membranes by 56% and 125% in 30 and 100 mg/kg haloperidol treatment groups, respectively. These increases in [3H] SCH 23390 binding to the membranes were restored to control levels after ceruletide treatment (100 micrograms/kg IP twice a day for 5 days). [3H] Spiperone binding to the rat striatal and cortical membranes also increased after chronic haloperidol treatment (by 66% and 99% in striatal membranes and by 27% and 62% in cortical membranes in the 30 and 100 mg/kg haloperidol treatment groups, respectively). Administration of ceruletide to haloperidol-treated rats reduced the increased [3H] spiperone binding to the cortical membranes toward the control level, but ceruletide was not effective in reducing the haloperidol-induced increase of [3H] spiperone binding to the striatal membranes. Activation of adenylate cyclase by dopamine (1 microM or 100 microM) or Gpp(NH)p (1 microM) was reduced in striatal and cortical membranes from haloperidol-treated rats. Ceruletide restored the lowered level of dopamine-stimulated or Gpp(NH)p-stimulated adenylate cyclase activity in the membranes from haloperidol-treated rats to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1992

Inhibitory effect of CCK-8 and ceruletide on glutamate-induced rises in intracellular free calcium concentrations in rat neuron cultures.

To study the mechanism by which cholecystokinin octapeptide (CCK-8) and its potent analogue, ceruletide, prevent glutamate-induced neuronal cell death in rat neuron cultures, we examined the effect of both peptides on glutamate-induced increases in the intracellular free calcium concentrations ([Ca2+]i), which are known to be a crucial trigger of the neurodegeneration induced by glutamate. CCK-8 itself did not alter [Ca2+]i in rat neuron cultures. Glutamate increased [Ca2+]i in neuron cultures rapidly and markedly. CCK-8 and ceruletide significantly suppressed the increases in [Ca2+]i induced by glutamate. The maximum inhibitory effects of CCK-8 and ceruletide at 10(-6) M reached 43 and 46% of the response to glutamate, respectively. Gastrin-I and CCK-4 also significantly attenuated the increases in [Ca2+]i induced by glutamate. The inhibitory effect of CCK-8 was completely blocked by the selective antagonist for CCK-B receptors, (+)L-365,260, but not by (-)L-364,718, which is a selective antagonist for CCK-A receptors. CCK-8 significantly suppressed [Ca2+]i response to kainate and high concentrations of extracellular K+, but not to N-methyl-D-aspartate. With cultured astrocytes, CCK-8 did not inhibit the increment of [Ca2+]i induced by glutamate. These findings clearly demonstrated that CCK-8 and ceruletide inhibit glutamate-induced increases in [Ca2+]i in neuron cultures through CCK-B receptors, suggesting that CCK-8 may participate in the central actions of glutamate.

Animals↗
PubMed1993

Ceruletide suppresses rotational behavior in lesioned rats via CCKA receptors.

The effects and pharmacological mechanisms underlying the inhibiting effect of ceruletide, a cholecystokinin (CCK)-related peptide, on apomorphine-induced turning behavior in 6-hydroxydopamine lesioned rats were investigated. For this purpose, selective CCKA and CCKB receptor antagonists were used. Ceruletide (50-400 micrograms/kg, s.c.) dose dependently suppressed apomorphine-induced rotational behavior. The antiapomorphine effect of ceruletide was reversed by the selective CCKA receptor antagonist, devazepide, but not by the selective CCKB receptor antagonist, L-365,260. This suggests that the suppression ceruletide exerts on hyperactive nigrostriatal dopamine neurons is mediated by CCKA receptors.

Animals↗
PubMed1993

Ceruletide, a cholecystokinin-like decapeptide, differentially reduces the stimulant effect of MK-801 and ketamine: evaluation by discrete shuttle avoidance in mice.

The non-competitive NMDA antagonist, MK-801 (dizocilpine: 0.03-0.3 mg/kg i.p.), a dissociative anesthetic, ketamine (1-20 mg/kg s.c.) and a CNS stimulant, methamphetamine (0.1-1 mg/kg s.c.), dose dependently increased the response rate in mice trained to discrete shuttle avoidance. MK-801 (0.1 mg/kg), ketamine (10 mg/kg) and methamphetamine (0.3 mg/kg) were almost equipotent. The cholecystokinin-like decapeptide, ceruletide, 0.1 micrograms/kg s.c., completely attenuated the response-increasing effect of MK-801 (0.1 mg/kg), although at this dose ceruletide alone did not produce any significant change in the avoidance response. Up to 10 micrograms/kg of ceruletide, which itself decreased the response rate, was required to reduce significantly the response-increasing effect of ketamine (10 mg/kg) and methamphetamine (0.3 mg/kg). On the other hand, haloperidol (0.01-0.1 mg/kg s.c.) decreased both the response rate and the % avoidance dose dependently, and inhibited the response-increasing effects of MK-801, ketamine and methamphetamine to almost the same degree. The present results suggest that comparatively lower doses of ceruletide inhibit selectively the stimulant effect of MK-801. Inhibition of dopamine release from the stored site in the nucleus accumbens may be mainly involved in this interaction.

Animals↗
PubMed1981

Central effects of ceruletide analogues.

Ten ceruletide analogues and cholecystokinin octapeptide (CCK-8) were compared with ceruletide regarding neuropharmacological effects in mice after peripheral administration. The effects under study were inhibition of motor response to noxious stimulation (hot plate), production of ptosis, inhibition of exploratory rearing activity, elevation of threshold for picrotoxin-induced convulsions, and antagonism of methylphenidate-induced gnawing. Desulfation, deamidation and shortening of the peptide chain by five amino acids destroyed all pharmacological activities of ceruletide. Other modifications were of unequal consequences for the pharmacological profile of a given analogue, decreasing some effects while increasing others. Hence, structural changes of the ceruletide molecule resulted in modulations of both potency and selectivity.

Analgesia↗
PubMed1985

Stimulatory action of (beta-Asp9) ceruletide on dog pancreatic exocrine secretion.

The synthetic analog of ceruletide, (beta-Asp9) ceruletide, which in previous studies was found to retain some central effects of ceruletide with virtually no effect on gallbladder contraction, was studied for its stimulatory effect on pancreatic secretion. This peptide was shown to induce an increase in the volume of pancreatic juice similar to that provoked by the parent compound. Its activity was 4% of that of ceruletide, as regards volume, dry residue and protein content of the pancreatic juice. It was concluded that the dissociation between central and peripheral effects concerned only the gallbladder contractility, since its potency as a pancreatic stimulant was of the same order of magnitude as that shown on the central nervous system.

Amino Acid Sequence↗