Disease relevance of Cck

• Cholecystokinin appears to play a contributory role in the development of pancreatitis [1].
• Since CCK can function as a satiety factor when administered to rodents, localization of Cckbr near the tub mutation identifies this receptor as a possible candidate gene for this obesity mutation [2].
• CCK-deficient mice are viable and fertile and exhibit normal body weight [3].
• This result demonstrates that CCK is not required for protein-induced pancreatic hypertrophy and increased proteolytic enzyme content [3].
• Finally, pertussis toxin inhibited the CCK-induced increase in the Ins-1,4,5-P3/PIP2 ratio in normal pancreatic islets [4].

Psychiatry related information on Cck

• Leptin, injected intraperitoneally (i.p.) at low doses (4-120 microg/kg), which did not influence feeding behavior for the first 3 hr postinjection, decreased food intake dose dependently by 47-83% during the first hour when coinjected with a subthreshold dose of CCK [5].
• These results demonstrate that centrally as well as peripherally administered CCK-8 suppresses locomotor activity in mice through an interaction with CCK-A, but not CCK-B, receptors [6].
• Small intestinal CCK levels in psychological stress mice were significantly lower than those in the control group (0.75+/-0.53 microg/g vs 1.98+/-1.17 microg/g, P<0.01), whereas plasma CCK concentrations were not different between the groups [7].
• Cholecystokinin-related peptides, after systemic or central administration, prevent carbon monoxide-induced amnesia in mice [8].
• Influence of the selective cholecystokinin antagonist L-364,718 on pain threshold and morphine analgesia [9].

High impact information on Cck

• Cells were significantly more sensitive to NAADP than to either cADPR or InsP3, whereas higher concentrations of NAADP selectively inactivated CCK-evoked Ca2+ signals in pancreatic acinar cells, indicating that NAADP may function as an intracellular messenger in mammalian cells [10].
• Excitation of the non-cholinergic nerves stimulates amylase secretion by a different intracellular coupling mechanism from that activated by cholinergic nerves or by peptides belonging to the cholecystokinin, gastrin or bombesin families [11].
• Straus and Yalow showed that brain CCK levels were reduced in the cerebral cortex of both genetically obese (ob/ob) and normal mice after a 2-5-day fast [12].
• We show here that fasting in mice significantly increases CCK binding due to an increased number of CCK receptors in the olfactory bulb and hypothalamus, but not in other brain regions [12].
• Cholecystokinin (CCK) is the parent molecule of a family of polypeptide hormones, some of which are secreted from the small intestine after food ingestion and stimulate both exocrine secretion and gall bladder contraction [12].

Chemical compound and disease context of Cck

• The effects of the cholecystokinin (CCK)-receptor antagonist proglumide, the protease inhibitor gabexate, and the hormones secretin and cholecystokinin-octapeptide (CCK-8) were studied in a model of acute hemorrhagic pancreatitis induced by feeding mice a choline-deficient, ethionine-supplemented (CDE) diet [1].
• Injection of nontoxic doses of CCK-8 before proglumide or gabexate injections completely abolished all beneficial effects and also increased the severity of pancreatitis due to CDE diet alone [1].
• In normal pancreatic islets, pertussis toxin inhibited the CCK-induced increase in Ins-1,4,5-P3, whereas no effect was seen at 3.3 mM glucose [4].
• Proglumide, a cholecystokinin receptor antagonist, exacerbates alloxan-induced diabetes mellitus in Swiss mice [13].
• CNTF treated lean animals had weight loss and decreased gallbladder contraction to acetylcholine and cholecystokinin compared to saline treated lean animals [14].

Biological context of Cck

• Both parietal cell number and level of H(+)/K(+)-ATPase messenger RNA (mRNA) were reduced in the mutant strains, but gastrin-CCK double-KO mice displayed more active parietal cells and larger acid output than the gastrin KO mice [15].
• Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice [5].
• The food-reducing effect of leptin injected with CCK was not associated with alterations in gastric emptying or locomotor behavior [5].
• Cholecystokinin levels in prohormone convertase 2 knock-out mouse brain regions reveal a complex phenotype of region-specific alterations [16].
• Here, we tracked CCK-expressing cells in the intestines and pancreata of normal mice (BALB/c), Non Obese Diabetic (NOD) mice and interferon (IFN)-gamma transgenic mice, which exhibit pancreatic regeneration, during embryonic development, the postnatal period and adulthood [17].

Anatomical context of Cck

• Altered control of gastric acid secretion in gastrin-cholecystokinin double mutant mice [15].
• BACKGROUND & AIMS: Three pathways control gastric acid secretion: the gastrin-enterochromaffin-like (ECL) cell axis, the vagus-parietal cell axis, and the cholecystokinin (CCK)-D cell axis [15].
• METHODS: Acid was measured after pylorus ligation, and biopsies from gastrin knockout (KO), gastrin-CCK double-KO, and wild-type (WT) mice were collected for biochemical, immunocytochemical, and electron-microscopic examination [15].
• In cerebral cortex, cortex-related structures and olfactory bulb, cholecystokinin levels were higher than wild type [16].
• Cholecystokinin levels were lower in hippocampus, septum, thalamus, mesencephalon, and pons in knock-out mice than wild-type mice [16].

Associations of Cck with chemical compounds

• These results indicate the existence of a functional synergistic interaction between leptin and CCK leading to early suppression of food intake which involves CCK-A receptors and capsaicin-sensitive afferent fibers [5].
• In contrast to amylase release, stimulation of acinar glucose transport by CCK or carbamylcholine was not augmented by VIP, secretin, IBMX or 8-Br-cyclic AMP [18].
• VIP, IBMX and 8-Br-cyclic AMP, all of which act through or mimic the action of cyclic AMP, potentiated the secretory response to maximal concentrations of CCK, carbamylcholine and the ionophore A23187, all of which act via intracellular calcium [18].
• The aim of this study was to investigate the effect of cholecystokinin (CCK) receptor antagonist on the abnormal behavior and dopamine (DA) transmission of tenascin (TN)-gene knockout mice [19].
• L-364,718 and L-365,260 did not alter LPS-induced decrease in social investigation, whatever the route of administration, suggesting that endogenous cholecystokinin does not mediate the effect of proinflammatory cytokines on social exploration in mice [20].

Physical interactions of Cck

• Studies of IGF II binding to acini at low temperature (15 degrees C) and binding to particulate fractions from acini were also consistent with the effect of insulin to increase and CCK8 to decrease the internalization of IGF II [21].
• Collectively, these data suggest that CCK interacts at the CCKB receptor to inhibit tonically the release and/or availability of an endogenous substance acting at opioid delta receptors [22].
• The results indicated galanin regulates CCK secretion by modulation of K+ ATP and cAMP production through receptors coupled to a PTX-sensitive G protein [23].

Co-localisations of Cck

• Prohormone convertase 2 is widely co-localized with cholecystokinin in rodent brain [16].

Regulatory relationships of Cck

• However, lack of both gastrin and CCK attenuated fasting-induced ghrelin expression and secretion [24].
• We also questioned whether IFN-gamma influences the expression of CCK [17].
• CONCLUSION: Psychological stress inhibits the small intestinal transit, probably by down-regulating CCK and up-regulating VIP expression in small intestine [7].
• Cholecystokinin-induced antinociception is not blocked by CCK-A or CCK-B receptor antagonists [25].
• CCK and A23187 did not alter the increase of cAMP induced by secretin and the inhibitory effect of octreotide on cAMP production [26].

Other interactions of Cck

• In the gastrin-CCK double-KO mice, acid secretion is only controlled by cholinergic vagal stimulation, which normalizes the acid output [15].
• The loss of prohormone convertase 2 alters CCK processing in specific brain regions [16].
• By contrast, in IFN-gamma transgenic mice, CCK expression was suppressed from birth to 3 months of age in the pancreata but not intestines [17].
• Levels of somatostatin and cholecystokinin in the brain of ataxic mutant mice [27].
• CCK and VIP levels in plasma and small intestine in mice were measured by radioimmunoassay (RIA) [7].

Analytical, diagnostic and therapeutic context of Cck

• Quantitative polymerase chain reaction measurements were performed to examine the relationship between peptide levels and cholecystokinin and enzyme expression [16].
• Molecular cloning of the mouse CCK gene: expression in different brain regions and during cortical development [28].
• VIP, Leu-enkephalin, CCK-8, angiotensin II, vasopressin, and neurotensin had no effect on the resting tension or on the response to transmural electrical stimulation [29].
• On gel-filtration chromatography and high-performance liquid chromatography (HPLC), this material coeluted with CCK 8 Gly [30].
• After treatment with carboxypeptidase B, the level of CCK Gly in Cpe(fat)/Cpe(fat) in these brain extracts was elevated to 33.5 ng/g, about 51-fold higher than in control [30].

References