Disease relevance of Cck

• The results suggest that the observed signaling pathways regulate parenchymal cell injury and death in CCK-induced pancreatitis [1].
• Rin5F cells, derived from a rat insulinoma, and STC-1 cells, derived from a murine intestinal tumor, process pro-CCK mainly to amidated CCK 8 [2].
• We conclude that CCK exerts protective activity against ethanol-induced damage and that this effect is mediated through specific CCKA receptors and hyperemia involving NO [3].
• Pretreating neostriatal neurons with 500 ng/ml pertussis toxin did not prevent CCK-8 from evoking cationic currents [4].
• Anti-inflammatory effects of leptin and cholecystokinin on acetic acid-induced colitis in rats: role of capsaicin-sensitive vagal afferent fibers [5].

Psychiatry related information on Cck

• Fasting blunted the satiety response to 3.0 microg/kg CCK, such that 30-min food intake was suppressed by 65.1% (relative to saline-treated controls) in fasted rats vs. 85.9% in the fed state (P < 0.05) [6].
• Differential role of cholecystokinin receptor subtypes in opioid modulation of ongoing maternal behavior [7].
• Regulation of cholecystokinin receptors in the hypothalamus of the rat: reciprocal changes in magnocellular nuclei induced by food deprivation and dehydration [8].
• These data suggest a previously unsuspected role for CCK in body weight regulation that may not depend entirely on reduction of feeding behavior and suggest a strategy for enhancing the effects of leptin in leptin-resistant obese individuals [9].
• Decrease in exploratory behavior in naturally occurring cholecystokinin (CCK)-A receptor gene knockout rats [10].

High impact information on Cck

• These results indicate that gastric leptin may be involved in early CCK-mediated effects activated by food intake, possibly including satiety [11].
• Characterization and inhibition of a cholecystokinin-inactivating serine peptidase [12].
• We demonstrate here that the administration of an antiemetic to rats significantly attenuates the food intake reduction caused by exogenously administered CCK but does not increase normal consumption [13].
• Moreover, the disappearance of gastrin from the pancreas during the first weeks after birth parallels the appearance of CCK in the intestine [14].
• Although phosphorylation has received most attention, tyrosine-O-sulphation is also common and has been closely investigated in the hormones gastrin and cholecystokinin (CCK) [14].

Chemical compound and disease context of Cck

• The inhibition of nitric oxide (NO) synthase by NG-nitro-L-arginine methyl ester attenuated the gastroprotection and gastric hyperemia induced by CCK while the concurrent treatment with L-arginine, but not D-arginine restored the protective activity of CCK and the accompanying increase in gastric blood flow [3].
• Similar to supraspinal neurotensin hyperalgesia, the hyperalgesia observed with i.t. CCK (30 ng) was inhibited by i.t. L-365260 (ID50 = 0.59 ng) at doses approximately 1000-fold less than that observed with i.t. devazepide (ID50 = 630 ng) [15].
• Somatostatin-, neuropeptide Y-, neurokinin B- and cholecystokinin-containing neurons were investigated in the rat hippocampus in two chronic models of temporal lobe epilepsy, i.e. 30 days after rapid kindling or electrically induced status epilepticus (post-status epilepticus) [16].
• Type B cholecystokinin receptors on rat glioma C6 cells. Binding studies and measurement of intracellular calcium mobilization [17].
• The results indicate that the calcium currents elicited in dorsal root ganglion neurons can be depressed by U50488H, an effect readily reversed by the kappa-opioid receptor antagonist Nor-BNI or by the antiopioid peptide CCK-8 [18].

Biological context of Cck

• The binding capacity of CCK-B receptors constitutes 34% of the total high affinity CCK binding sites [19].
• We found that caspases not only mediate apoptosis but also regulate other parameters of CCK-induced acinar cell injury that are characteristic of pancreatitis; in particular, caspases negatively regulate necrosis and trypsin activation in acinar cells [1].
• Several affected cell lines displayed about 80% reduction in CCK content in early passages after transfection [2].
• Although cholecystokinin A (CCK-A) receptors (CCK-AR) mediate the feeding inhibitory actions of CCK in both rats and mice, the absence of CCK-AR results in species-specific phenotypes [20].
• Under current-clamp recordings, CCK-8 depolarized DA neurons and triggered action potentials [21].

Anatomical context of Cck

• Gastrin (CCK-B) receptors, which were not detected in normal rat pancreas, constitute about one third of the total high affinity CCK receptors [19].
• In the present work, using biochemical approaches we have identified and characterized CCK antagonist binding sites in pancreatic plasma membranes [22].
• Cholecystokinin modulates the release of dopamine from the anterior and posterior nucleus accumbens by two different mechanisms [23].
• CCK levels were decreased 62% in hippocampus, 53% in amygdala and 57% in pons-medulla in PC1 knockout mice as compared to controls [24].
• NC and CCK did not coexist in the dentate gyrus; however, 9% of the NC-IR cells in the CA fields also contained CCK [25].

Associations of Cck with chemical compounds

• The intracerebroventricular administration of the nonselective CCK receptor agonist caerulein or the selective CCK-B receptor agonist pentagastrin increased dose dependently the level of anxiety [26].
• In the present study, we investigated gastrin (CCK-B) receptor expression in the azaserine-induced rat pancreatic carcinoma DSL-6, comparing it to normal rat pancreas, and we also characterized CCK receptor subtypes in this tumor [19].
• Histologic examination verified that lesions with NMDA agonists produced relative sparing of NADPH-diaphorase, SS, VIP, and CCK neurons [27].
• The effect of devazepide was prevented by cholecystokinin octapeptide (CCK-8; 40 micrograms kg-1, s.c) as well as by the selective glucocorticosteroid GII receptor agonist, dexamethasone (30 micrograms kg-1, s.c.) 4 [28].
• Pharmacology of a cholecystokinin receptor on 5-hydroxytryptamine neurones in the dorsal raphe of the rat brain [29].

Physical interactions of Cck

• Thus, Lys120 outside the TM2 and Arg352 outside the TM6 of the CCK-AR are amino acids interacting with Tyr[SO(3)H]27 and Asp32 of the CCK peptide for binding [30].
• The mutated receptor displayed similar expression levels and high affinity CCK binding compared with the wild type CCKBR [31].
• Our data confirmed that the control of the exocrine function of the pancreas is complex, and that it involves peptides such as the cholecystokinin/gastrin-like peptides, bombesin-like peptides and somatostatin [32].
• Cholecystokinin-binding sites are localized in the main olfactory bulb, on neurons in the cortical "hindlimb" and "forelimb" region, in the hippocampus, and in the cingulate and visual cortex [33].
• The ability of somatostatin analogs to interact with the binding of cholecystokinin has been studied in pancreatic and brain cortical membranes [34].

Enzymatic interactions of Cck

• Cholecystokinin octapeptide and the C-terminal tetrapeptide are hydrolysed by a highly purified preparation of "enkephalinase" (EC 3.4.24.11) [35].

Co-localisations of Cck

• Thus galanin-like immunoreactivity sometimes also co-localized with cholecystokinin- and neuropeptide tyrosine-like immunoreactivities in calcitonin gene-related peptide-immunoreactive terminals and in some large dense-core vesicles in such terminals [36].
• 1. Cholecystokinin is co-localized within the oxytocin- and, to a lesser extent, vasopressin-synthesizing magnocellular neurones in the hypothalamic supraoptic and paraventricular nuclei [37].

Regulatory relationships of Cck

• Leptin deficiency induced by fasting impairs the satiety response to cholecystokinin [6].
• We found that both CCK-induced satiety and its ability to increase c-Fos-like-immunoreactivity in key brainstem-feeding centers were attenuated by NPY pretreatment [6].
• A moderate to high percentage of CCK mRNA-positive neurons express PC1 mRNA [24].
• Vasoactive intestinal polypeptide stimulates cholecystokinin secretion in perfused rat duodenum [38].
• The CCKB selective agonist, pentagastrin, was inactive when applied at concentrations up to 10 microM. the CCKA receptor antagonist L-364,718 (1 to 100 nM) blocked the response to cholecystokinin [29].

Other interactions of Cck

• Prohormone convertase 1 is necessary for the formation of cholecystokinin 8 in Rin5F and STC-1 cells [2].
• In a previous study, we developed a new antagonist radioligand, 125I-Bolton-Hunter-labeled JMV-179, for the CCK-A receptor (CCK-AR), to analyze CCK antagonist binding sites in pancreatic plasma membranes [22].
• SS mRNA and peptide levels significantly decreased in the PC/RSC and hippocampus but not in the frontal cortex 3 days after 0.5 mg/kg MK-801 treatment whereas CCK mRNA and peptide levels significantly decreased in all of the brain regions examined [39].
• Varicose fibers in this nucleus also contained these peptides in addition to CCK, GAD, TH, 5HT, and NPY [40].
• PC2 knockout mouse brains had less CCK 8 than wild-type, although a substantial amount of CCK was still present [41].

Analytical, diagnostic and therapeutic context of Cck

• Constitutive expression of antisense PC1 message in stably transfected Rin5F cells resulted in a significant reduction of the cellular content of CCK 8 as measured by radioimmunoassay [2].
• Their colocalization with CCK mRNA was examined using double-label in situ hybridization [41].
• 3. Intravenous infusion of CCK-8 or gastrin-17 (8-200 pmol min-1) increased gastric mucosal blood flow in a dose-dependent fashion [42].
• Cholecystokinin octapeptide (CCK-8) antagonizes morphine analgesia in nucleus accumbens of the rat via the CCK-B receptor [43].
• Transmural nerve stimulation (TNS, 200 mA, 0.2 ms, 8 and 16 Hz) elicited an increase in perfusion pressure reflecting contraction of the bed and CCK inhibited neurogenic contractions elicited by 8 and 16 Hz TNS [44].

References