Study into the role of cholecystokinin in bombesin-stimulated pancreatic growth in rats and hamsters.

The effects of cholecystokinin and bombesin on growth of the exocrine pancreas have been studied extensively in rats but not in hamsters. Since hamsters are frequently used for studying pancreatic carcinogenesis it seems highly relevant to determine the effects of these peptides on growth of the hamster pancreas as well. In order to determine whether or not bombesin stimulates pancreatic growth in hamsters and to investigate the role of cholecystokinin in mediating this effect, we conducted a 2-week experiment in which cholecystokinin and bombesin were administered to both rats and hamsters, either with or without lorglumide (CR-1409; a specific cholecystokinin receptor antagonist).

Influence of cholecystokinin antagonist on the effects of cholecystokinin and bombesin on azaserine-induced lesions in rat pancreas.

Both cholecystokinin and bombesin have been shown to promote pancreatic carcinogenesis in the azaserine-rat model. The present study was undertaken to discriminate between the effects of cholecystokinin and bombesin and to establish the modulating properties of the specific cholecystokinin receptor antagonist CR-1409 on pancreatic carcinogenesis. After initiation with 30 mg/kg of azaserine, six groups of 15 Wistar rats were treated for 16 wk with cholecystokinin, bombesin, or gelatin (control), some in combination with CR-1409.

[Administration of cytostatic drugs by intra-arterial route. Theoretical basis].

The Authors discuss the theoretical principles of the intra-arterial administration route of antineoplastic drug in the treatment of primaries or metastatic diseases.

[Indications for regional lymphadenectomy in skin melanomas: a problem still in debate. Personal experience and review of the literature].

The Authors discuss indications to the regional dissection on the basis of personal experience and data reported in the literature concluding for the lack of specific advantages for elective operations.

Antiproliferative effects of gastrin receptor antagonists and antibodies to gastrin on human colon carcinoma cell lines.

The gastrointestinal hormone gastrin has been shown to stimulate the growth of normal colonic mucosa. To examine for a possible role of gastrin in the proliferation of cultured colon tumor cells, we have studied the effects of two gastrin receptor antagonists, proglumide and benzotript, and of antibodies to gastrin. We find that proglumide (50% effective concentration, 2 to 5 mM) and benzotript (50% effective concentration, 0.

Bioavailability of 125I bromelain after oral administration to rats.

Bromelain is a sulphydral protease, derived from the stem and fruit of pineapples. Semi-purified preparations of bromelain are used in the treatment of inflammation and oedema. There is however no unequivocal proof of the absorption of the enzyme after oral administration.

Pharmacokinetics of loxiglumide after single intravenous or oral doses in man.

Loxiglumide (D,L-4-(3,4-dichlorobenzoylamino)-5-(N-3-methoxypropyl-pentylam ino)-5-oxo-pentanoic acid, CR 1505) was given intravenously to 8 male healthy volunteers in a single dose of 2 mg/kg body weight (b.w.) or orally in a single dose of 5 mg/kg b.

Calcium antagonists: vinylogues and bivalent ligands related to nifedipine.

The synthesis and the pharmacological properties of some vinylogues and bivalent ligands related to nifedipine are described.

Chronic intrathecal cannulation affects hypothalamic beta-endorphin and met-enkephalin concentrations.

Beta-endorphin concentrations decrease and met-enkephalin concentrations increase in the hypothalamus of rats bearing a chronic intrathecal cannula. The modification of the concentrations of beta-endorphin is already present on day 1 after surgery, whereas met-enkephalin is affected starting on day 6, and both peptides are still modified on day 10. These results indicate that chronically cannulated rats are not to be considered normal animals.

[Postoperative external biliary fistulas: personal case series].

Over the period 1974-1986, five patients with external biliary fistulas were admitted to our clinic. The fistulas set in as complications of surgical operations due in 3 cases to a Kehr drainage of the common bile duct, in 1 case to drainage of a subhepatic abscess and in 1 case to pancreatic hydatid cyst. The causes of onset of the fistulas are reported as well as the therapy adopted in each case.

Pharmacological properties of lorglumide as a member of a new class of cholecystokinin antagonists.

Derivatives of 5-(dipentylamino)-5-oxo-pentanoic acid are a new class of non-peptide cholecystokinin (CCK) antagonists. The most potent compound, D,L-4-(3,4-dichlorobenzoylamino)-5-(dipentylamino)-5-oxo-pen tanoic acid (lorglumide, CR 1409), has a great affinity for the pancreatic CCK receptors and is a competitive, specific and potent CCK antagonist on the smooth muscles of the gall bladder and ileum of the guinea pig and on the CCK-induced amylase secretion of isolated pancreatic acini. In vivo lorglumide antagonizes the contraction of the gall bladder of the guinea pig and of the dog provoked by i.

Effect of a cholecystokinin antagonist on some effects of diazepam.

Dose responses were evaluated for the effects of diazepam alone or together with the cholecystokinin receptor antagonist CR 1409 on pentetrazole-induced convulsions, motor performance and spontaneous motor activity. The results obtained showed that the cholecytokinin antagonist potentiated the effects of diazepam on motor performance and the anticonvulsant activity of diazepam, while it did not affect spontaneous motor activity. The data presented are consistent with a role for cholecystokinin in some effects of diazepam.

Pharmacological characterisation of a new potent and specific nonpolypeptidic cholecystokinin antagonist.

D,L-4-(3,4-Dichloro-benzoylamino)-5-(N-3-methoxypropyl- pentylamino)-5-oxo-pentanoic acid (CR 1505) belongs to a newly discovered class of agents with cholecystokinin (CCK) antagonistic activity. CR 1505 displaces CCK-8 from the central CCK receptors at concentrations of 9.1 mumol/l, and from the peripheral CCK receptors at concentrations of 0.

Dissociation of tolerance and dependence to morphine: a possible role for cholecystokinin.

Since cholecystokinin (CCK) has been suggested to be an endogenous opiate antagonist, we tried to evaluate if this peptide could be involved in the development of tolerance to morphine. Naive rats were chronically administered morphine, either alone or concomitantly with proglumide or benzotript, two putative CCK receptor antagonists. Chronic treatments with both CCK antagonists alone were also established.

Antispasmodic activity on the gallbladder of the mouse of CR 1409 (lorglumide) a potent antagonist of peripheral CCK.

Cholecystokinin (CCK) is a hormonal regulator of the motility of the gallbladder. CCK-8, i.e.

Different peripheral and central antagonistic activity of new glutaramic acid derivatives on satiety induced by cholecystokinin in rats.

New glutaramic acid derivatives with cholecystokinin antagonistic activity were evaluated for their capacity to inhibit the satiety effect induced in the rat by intraperitoneal (i.p.) injection of cholecystokinin octapeptide (CCK-8).

Structural features of various proglumide-related cholecystokinin receptor antagonists.

Thirteen proglumide derivatives that varied in the length of the di-n-alkyl group and in the substitutions on the benzoyl moiety were tested for their ability to interact with guinea pig pancreatic cholecystokinin (CCK) receptors. Each derivative was more potent than proglumide. There was a close correlation between their abilities to inhibit CCK-stimulated amylase release and to inhibit binding of 125I-CCK.