Disease relevance of Cckbr

• Spinal effect of the cholecystokinin-B receptor antagonist CI-988 on hyperalgesia, allodynia and morphine-induced analgesia in diabetic and mononeuropathic rats [1].
• In situ hybridization showed that RTX treatment caused a marked and significant increase in the number of dorsal root ganglion (DRG) neurone profiles expressing CCKB receptor mRNA, whereas only a small increase was observed for CCKA receptor mRNA expressing neurone profiles [2].
• Prevention of tolerance to the antinociceptive effects of systemic morphine by a selective cholecystokinin-B receptor antagonist in a rat model of peripheral neuropathy [3].
• The rat C6 glioma cell line may serve as a useful model for studying CCKB receptor in brain [4].
• Central microinjection of CCK in rats induced a thermogenic response that could be attenuated by CCKB receptor antagonists, but some authors observed a hypothermia [5].

Psychiatry related information on Cckbr

• The present study was undertaken to determine whether peripheral injections of antagonists of the CCK1 receptor (lorglumide) and the CCK2 receptor (L-365,260) can influence the effects of morphine on maternal behavior during lactation [6].
• We investigated, by c-Fos immunohistochemistry, the effect of CCK1 and CCK2 receptor antagonists (SR-27,897 and L-365,260, respectively) on c-Fos levels expression induced by food deprivation [7].
• L-365,260 [3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4- benzodiazepine-3-yl)-N'-(3-methylphenylurea)], a potent nonpeptide antagonist of the CCKB receptor, is currently under investigation to treat anxiety and panic disorders [8].
• Cholecystokinin-B receptor antagonists attenuate morphine dependence and withdrawal in rats [9].
• Effect of CCK1 and CCK2 receptor blockade on amphetamine-stimulated exploratory behavior and sensitization to amphetamine [10].

High impact information on Cckbr

• Furthermore, CI 988, an antagonist of the CCK-B receptor, chronically coadministered with morphine, reduces autotomy, a behavior that may be a sign of neuropathic pain following peripheral nerve section [11].
• Here we demonstrate that cholecystokinin acting at the cholecystokinin-B receptor is required for associative but not non-associative morphine tolerance [12].
• RESULTS: CCK2 receptor mRNA and proteins were found abundantly in human pancreatic islets in normal pancreas and chronic pancreatitis [13].
• METHODS: Tissue samples of normal human pancreas, chronic pancreatitis, and ductal pancreatic carcinomas were investigated under carefully controlled conditions for expression of CCK1 and CCK2 receptor messenger RNA (mRNA) and proteins using in situ hybridization and in vitro CCK receptor autoradiography by means of subtype-selective analogues [13].
• Mitogenic effects of gastrin I on ductal complexes in vivo and of tetragastrin, pentagastrin, and gastrin I and II, with or without the CCK-B receptor antagonist L-365,260, on duct-like cells in vitro were analyzed by 5-bromo-2'-deoxyuridine labeling [14].

Biological context of Cckbr

• COS-7 cells transfected with this cDNA expressed binding sites for agonists and antagonists characteristic of a CCKB receptor subtype [15].
• These findings provided the first evidence for an autocrine/paracrine role of CCK and gastrin on stimulation of GH3 cell growth through the CCK-B receptor [16].
• These results suggest that CCK mediates vasodilatation of the mesenteric vascular bed through the release of NO via its presynaptic CCK2R [17].
• Gene expression of CCK-AR and CCK-BR significantly increased in myocardium of ES rats [18].
• L-365, 260, a selective CCKB receptor antagonist, did not alter the OT-induced inhibition of gastric emptying [19].

Anatomical context of Cckbr

• In the central nervous system there is evidence for CCKA and CCKB receptor subtypes [15].
• Northern blot analysis revealed a significant expression of CCK-B receptor mRNA in GH3 cells, but not in normal rat pituitary glands [16].
• The levels of CCK-2 receptor mRNA in the mucosa of the glandular stomach were determined by Northern blot analysis [20].
• It provides evidence that CCK2R are lacking or not functional in the gastrointestinal tract of rats [21].
• By in situ hybridization, however, only the signals of CCK-BR but not CCK-AR were detected in the lung, and the positive staining was only found in vascular endothelial cells and macrophages [22].

Associations of Cckbr with chemical compounds

• The selective CCK-B receptor antagonists CI-988 (PD 134308) and L-365,260 produced anxiolytic-like effects, whereas MK-329, a CCK-A receptor antagonist, was respectively less potent by factors of 313 and 200 [23].
• 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 [23].
• Cholecystokinin tetrapeptide (CCK-4), a selective CCKB receptor agonist, also evoked cationic currents [24].
• The inhibition of neurogenic contractions was blocked by the CCK2 receptor (CCK2R) antagonist, L-365,260 (10 and 100 nM), but not by the CCK1R antagonist, SR-27897 [17].
• The effects of intrathecally administered FK480, a cholecystokinin-A receptor antagonist, and YM022, a cholecystokinin-B receptor antagonist, on the formalin test in the rat [25].

Physical interactions of Cckbr

• The mutated receptor displayed similar expression levels and high affinity CCK binding compared with the wild type CCKBR [26].

Regulatory relationships of Cckbr

• The results suggest that CCK antagonism of opioid-induced disruption of maternal behavior occurs due to the action of CCK on both CCK1 and CCK2 receptor subtypes [6].
• We examined whether the CCK-A and CCK-B receptor genes are expressed in the islets and the role of CCK-A receptor in insulin secretion [27].
• The results showed a good correlation between the binding of gastrin to CCKB receptor [Kd 1.125 +/- 0.3 (SD) nM] and its ability to either induce ornithine decarboxylase activity [50% effective concentration, 0.6 +/- 0.3 nM] and [3H]-thymidine incorporation [50% effective concentration, 2 +/- 0.4 nM] [28].
• Blockade of gastrin/CCKB receptors partially inhibits intragastric meal-stimulated acid secretion indicating that the gastrin/CCKB receptor has a physiological role as mediator of food-stimulated acid secretory response in conscious rats [29].

Other interactions of Cckbr

• To gain a better understanding of the roles of CCK-A and CCK-B receptors in spinal nociceptive transmission during inflammation, this study evaluated the effects of intrathecally administered FK480 (a CCK-A receptor antagonist) and YM022 (a CCK-B receptor antagonist) [25].
• Paracrine stimulation of cell growth by cholecystokinin/gastrin through cholecystokinin-B receptor on GH3 cells in vitro [16].
• The cholecystokinin B receptor (CCK(B)R) is localized on pancreatic endocrine somatostatin delta-cells [30].
• CCK-8s-induced reduction in the score and WWI was prevented by CCK-A, but not by CCK-B receptor antagonist, whereas neither antagonist altered the inhibitory effect of leptin on colitis-induced injury [31].
• ES reduced all colonic damage scores (p < 0.05-0.01), while central CRF (p < 0.05-0.001) and CCKB receptor (p < 0.05-0.01) blockers or peripheral hexamethonium (p < 0.05-0.01) and RU-486 (p < 0.05) reversed stress-induced improvement [32].

Analytical, diagnostic and therapeutic context of Cckbr

• METHODS: CCK-AR and CCK-BR mRNA expression and cellular distribution in the rat lung were detected by highly sensitive method of in situ reverse transcription-polymerase chain reaction (RT-PCR) and conventional in situ hybridization [22].
• Southern blot analysis of RT-PCR amplified CCK-AR and CCK-BR mRNA products using [gamma-32P]ATP 5'-end-labelled probe showed specific hybridization bands [33].
• 2. Intravenous injection of CAM-1481 (1 mg kg-1), a dipeptoid antagonist of CCKA receptors, or CAM-1028, a dipeptoid CCKB receptor antagonist (1 mg kg-1), had no effect on basal gastric mucosal blood flow as determined by the clearance of hydrogen in urethane-anaesthetized rats [34].
• Hypophysectomy 5 days prior to sacrifice, resulting in a nerve lesion in the neurohypophysial pathway and removal of the anterior pituitary hormones, induced a significant increase in CCKB receptor mRNA levels in neurons of the PVN [35].
• The response was not decreased by atropine, hexamethonium, vagotomy, a mixture of adrenoceptor antagonists (prazosin + idazoxan + propranolol), or by the CCKB receptor antagonist L365,260 [36].

References