Chronic oral administration of protease inhibitor decreases CCK-A receptor mRNA expression but increases pancreatic growth in rats. 2001

K Fukumitsu, and H Nakamura, and M Otsuki
Third Department of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyusyu.

It is well-known that chronic oral administration of trypsin inhibitors induces pancreatic hypertrophy and hyperplasia via stimulation of endogenous cholecystokinin (CCK) release. Because the growth-promoting effect of CCK on the pancreas is specifically mediated by the CCK-A receptor, we examined the plasma CCK concentrations, the expression of CCK mRNA in the intestine and CCK-A receptor mRNA in the pancreas, and pancreatic growth in rats after chronic oral administration of synthetic protease inhibitor (PI). PI at a dose of 100 mg/kg body weight was administered via an orogastric tube once daily for 20 days. Plasma CCK concentrations at 24 hours after the first PI administration were significantly higher than those in randomly fed rats (6.57 +/- 0.67 pmol/L vs 4.31 +/- 0.51 pmol/L; p < 0.001), and further increased to 14.24 +/- 1.63 pmol/L after PI for 10 days and decreased to 10.05 +/- 0.72 pmol/L after 15 days of PI administration. Treatment with PI for 20 days significantly increased the pancreatic weight, and the total pancreatic protein and DNA content by 190%, 290%, and 170%, respectively, when compared to the control rats. Chronic oral administration of PI, however, reduced CCK-A receptor mRNA expression in the pancreas by 60%. These findings suggest that chronic oral administration of PI induces an elevation of endogenous CCK release and stimulates pancreatic growth, but down-regulates the biosynthesis of CCK-A receptor at the transcriptional level in the pancreas.

UI MeSH Term Description Entries
D008297 Male Males
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D010179 Pancreas A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.
D011949 Receptors, Cholecystokinin Cell surface proteins that bind cholecystokinin (CCK) with high affinity and trigger intracellular changes influencing the behavior of cells. Cholecystokinin receptors are activated by GASTRIN as well as by CCK-4; CCK-8; and CCK-33. Activation of these receptors evokes secretion of AMYLASE by pancreatic acinar cells, acid and PEPSIN by stomach mucosal cells, and contraction of the PYLORUS and GALLBLADDER. The role of the widespread CCK receptors in the central nervous system is not well understood. CCK Receptors,Caerulein Receptors,Cholecystokinin Octapeptide Receptors,Cholecystokinin Receptors,Pancreozymin Receptors,Receptors, CCK,Receptors, Caerulein,Receptors, Pancreozymin,Receptors, Sincalide,Sincalide Receptors,CCK Receptor,CCK-4 Receptors,CCK-8 Receptors,Cholecystokinin Receptor,Receptors, CCK-4,Receptors, CCK-8,Receptors, Cholecystokinin Octapeptide,CCK 4 Receptors,CCK 8 Receptors,Octapeptide Receptors, Cholecystokinin,Receptor, CCK,Receptor, Cholecystokinin,Receptors, CCK 4,Receptors, CCK 8
D002766 Cholecystokinin A peptide, of about 33 amino acids, secreted by the upper INTESTINAL MUCOSA and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. Pancreozymin,CCK-33,Cholecystokinin 33,Uropancreozymin
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000501 Allylglycine An inhibitor of glutamate decarboxylase and an antagonist of GAMMA-AMINOBUTYRIC ACID. It is used to induce convulsions in experimental animals. 2-Amino-4-Pentenoic Acid
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001550 Benzamidines Amidines substituted with a benzene group. Benzamidine and its derivatives are known as peptidase inhibitors.
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated

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