Different actions of CCK on pancreatic and gastric growth in the rat

Effect of CCK(A) receptor blockade

G. Varga, Krisztina Kisfalvi, Iva Pelosini, Massimo D'Amato, Carmelo Scarpignato

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

1. It is now well established that cholecystokinin (CCK) has a major physiological role in the regulation of pancreatic secretion and gastro-intestinal (GI) motility. Both these actions are mediated by stimulation of CCK(A)-receptors located on pancreatic acini and GI smooth muscle cells. While chronic administration of CCK-like peptides invariably causes pancreatic hypertrophy and hyperplasia, their action on gastric growth remains controversial. 2. In the present investigation the action of exogenous and endogenous CCK on both pancreatic and gastric growth was studied in the same animal. In addition, the ability of dexloxiglumide, a new potent and selective CCK(A)-receptor antagonist, to counteract CCK-mediated effects was evaluated. 3. The amphibian peptide caerulein (1 μg kg-1 intraperitoneally three times daily) was used as a CCK agonist, while camostate (200 mg kg-1 intragastrically once daily), a synthetic protease inhibitor, was used to release endogenous CCK. They were administered to rats for seven days with or without dexloxiglumide (25 mg kg-1 subcutaneously 15 min before the stimulus). On the eighth day, animals were killed, the pancreas and stomach excised, weighed, homogenized and their protein and DNA content measured. 4. Both exogenous and endogenous CCK increased the weight of the pancreas as well as the total pancreatic protein and DNA content. Dexloxiglumide, which alone did not affect pancreatic size and composition, was able to counteract both caerulein- and camostate-induced pancreatic changes. Neither stimuli affected gastric growth in respect of weight and composition of the oxyntic gland area and the antrum. 5. These results show different effects of CCK on pancreatic and gastric growth. The CCK-induced pancreatic hypertrophy and hyperplasia are blocked by the potent and specific CCK(A)-receptor antagonist, dexloxiglumide. This compound therefore represents a useful tool to investigate CCK-receptor interactions in peripheral organs.

Original languageEnglish
Pages (from-to)435-440
Number of pages6
JournalBritish Journal of Pharmacology
Volume124
Issue number3
DOIs
Publication statusPublished - 1998

Fingerprint

Cholecystokinin A Receptor
Cholecystokinin
Stomach
Growth
Ceruletide
Hypertrophy
Hyperplasia
Pancreas
Cholecystokinin Receptors
Weights and Measures
Peptides
Gastrointestinal Motility
DNA
Amphibians
Protease Inhibitors
Smooth Muscle Myocytes
Proteins

Keywords

  • CCK
  • CCK-antagonists
  • CCK-receptors
  • Dexloxiglumide
  • Gastric growth
  • Pancreatic growth

ASJC Scopus subject areas

  • Pharmacology

Cite this

Different actions of CCK on pancreatic and gastric growth in the rat : Effect of CCK(A) receptor blockade. / Varga, G.; Kisfalvi, Krisztina; Pelosini, Iva; D'Amato, Massimo; Scarpignato, Carmelo.

In: British Journal of Pharmacology, Vol. 124, No. 3, 1998, p. 435-440.

Research output: Contribution to journalArticle

Varga, G. ; Kisfalvi, Krisztina ; Pelosini, Iva ; D'Amato, Massimo ; Scarpignato, Carmelo. / Different actions of CCK on pancreatic and gastric growth in the rat : Effect of CCK(A) receptor blockade. In: British Journal of Pharmacology. 1998 ; Vol. 124, No. 3. pp. 435-440.
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