Different actions of CCK on pancreatic and gastric growth in the rat: effect of CCK_A receptor blockade

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 e ects was evaluated. 3 The amphibian peptide caerulein (1 mg kg 71 intraperitoneally three times daily) was used as a CCK agonist, while camostate (200 mg kg 71 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 71 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 a ect pancreatic size and composition, was able to counteract both caerulein-and camostate-induced pancreatic changes. Neither stimuli a ected gastric growth in respect of weight and composition of the oxyntic gland area and the antrum. 5 These results show di erent e ects of CCK on pancreatic and gastric growth. The CCK-induced pancreatic hypertrophy and hyperplasia are blocked by the potent and speci®c CCK A -receptor antagonist, dexloxiglumide. This compound therefore represents a useful tool to investigate CCKreceptor interactions in peripheral organs.

Exocrine pancreatic pathology in female Harlan Sprague-Dawley rats after chronic treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin-like compounds.

“…The observed acinar atrophy of the pancreas may be related in part to the down-regulation of CCK, an important regulator of pancreatic growth and function (Baldwin 1995;Varga et al 1998). As shown by Lee et al (2000) in samples from the present PCB-126 study, levels of intestinal CCK are reduced by PCB-126 exposure.…”

Hormonal and neural regulation of intestinal function in pigs

“…Epidermal growth factor (EGF), and transforming growth factor-α (TGF-α) and their respective receptors are abundant in fetal GI tissues though no convincing data on their trophic effects could be found (Menard et al, 1988). The GI endocrine system produces some gut regulatory peptides in the prenatal period (Guilloteau et al, 1998) but studies on the role of gastrin releasing peptide (GRP) and cholecystokinin (CCK) did not confirm their effect on the fetal pancreas (Dembiński et al, 1990;Varga et al, 1998). The prenatal phase of development affects the postnatal function of the gastrointestinal tract, particularly during the first few postnatal days.…”

CCK₁ Antagonists: Are They Ready for Clinical Use?

“…A few years back we asked ourselves the question whether the physiological application of these compounds would be useful in clinical practice [3] . Since then, comprehensive reviews on the biological actions of CCK [4,5] and on CCK receptors [6] have been pub-…”