Disease relevance of Cckar

• CONCLUSION: These results suggest that CCK-1R contributes to pancreatic regeneration after acute haemorrhagic pancreatitis and that tubular complexes are involved in the process of acinar cell regeneration following pancreatic injury [1].
• We investigated the serial changes in CCK-1R mRNA and protein levels and their immunolocalization after acute haemorrhagic pancreatitis induced in male Wistar rats by retrograde intraductal infusion of 4% sodium taurocholate (100 micro L 100 g(-1) body weight) [1].
• Therefore, we characterized CCK binding properties and CCK-A receptor mRNA expression in pancreatic carcinomas and dysplastic pancreata from the Tg(Ela-1, SV40E+Ela-1, neo)Bri19 strain of ELSV transgenic mice [2].
• 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 [3].
• Intrathecal administration of the selective CCKB receptor antagonist L-365260 dose-dependently inhibited neurotensin hyperalgesia from the RMg (ID50 = 0.42 ng) at doses approximately 1000-fold less than that observed with the selective CCKA receptor antagonist devazepide (ID50 = 646 ng) [4].

Psychiatry related information on Cckar

• To determine the role of CCK-A receptors in the cholecystokinin (CCK)-induced suppression of locomotor activity in the rat, the ability of the selective CCK-A receptor antagonist L364,718 to block these responses was investigated [5].
• 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].
• 1. The effect of the CCKA receptor antagonist, devazepide (100 mg kg-1) on meal parameters during the initial phase of the dark period was studied in free-feeding rats by use of a procedure for continuously monitoring feeding patterns [7].
• Effect of intracerebroventricular and systemic injections of caerulein, a CCK analogue, on electrical self-stimulation and its interaction with the CCKA receptor antagonist, L-364,718 (MK-329) [8].
• Intracerebroventricular cholecystokinin A-receptor antagonist does not reduce satiation by endogenous CCK [9].

High impact information on Cckar

• The ethanol-induced increase in amylase output can be completely inhibited by the CCK-A receptor antagonist L-364,718 and partially inhibited by the muscarinic cholinergic antagonist atropine [10].
• CCK1 receptor proteins were found occasionally in small-sized pancreatic nerves, whereas acini expressed a low density of CCK2 receptors in a few cases of chronic pancreatitis [11].
• CCK-A receptor may mediate reflexes stimulated by CCK through the release of other transmitters from neurons bearing the receptor [12].
• Many CCK-A receptor myenteric neurons contained the inhibitory transmitter vasoactive intestinal polypeptide, and some were immunoreactive for the excitatory transmitter substance P [12].
• CCK-A receptor immunoreactivity was localized to myenteric neurons and to fibers in the muscle and mucosa [12].

Chemical compound and disease context of Cckar

• 3. Both the pressor response and bradycardia elicited by sCCK-8 were reduced by the selective CCKA receptor antagonists, devazepide (0.5-50 nmol kg-1) and lorglumide (1-7 mumol kg-1) [13].
• Administration of the selective CCKB receptor antagonist L-365260 i.t. dose-dependently inhibited mustard oil hyperalgesia (ID50 = 364 ng) at doses approximately 5-fold less than the CCKA receptor antagonist devazepide (ID50 = 1760 ng) [14].
• Administration of atropine (3 mg/kg, s.c.) or a CCK1-receptor antagonist, Z-203 (0.1 mg/kg, i.v.), inhibited food-stimulated or CCK-8-induced (1 microg/kg, s.c.) enhancement of pancreatic exocrine secretion and exacerbation after the development of PBDL-induced pancreatitis [15].
• A bolus injection of the CCK A receptor antagonist, loxiglumide, CR 1505 (0.1, 0.5 and 1.0 mg/kg ip), prior to clinimeal blocked the inhibitory action of CCK on the motor activity in a concentration-dependent manner [16].
• We examined whether the short-term administration of KSG-504 (KSG), a synthetic CCK-A receptor antagonist, inhibited the regeneration of pancreatic acinar cells after ethionine-induced acute pancreatitis in rats [17].

Biological context of Cckar

• The binding of 125I-ASA-JMV-179 to plasma membranes was inhibited by JMV-179 (IC50, 6 +/- 2 nM), by (Thr28, Ahx31)-CCK-25-33 (IC50, 1.2 +/- 0.5 nM), and by the nonpeptide CCK-AR antagonist L-364,718 (IC50, 2 +/- 1 nM) [18].
• Photoaffinity labeling of rat pancreatic cholecystokinin type A receptor antagonist binding sites demonstrates the presence of a truncated cholecystokinin type A receptor [18].
• These data, and the localization of the labeled fragments in the amino acid sequence of the receptor, suggest that the 47-50-kDa protein represents a CCK-AR lacking its amino-terminal extracellular domain.(ABSTRACT TRUNCATED AT 400 WORDS)[18]
• The gene overexpression of the CCK-A receptor and the novel gene expression of the gastrin (CCK-B) receptor may be generated by alterations in gene regulation during carcinogenesis, and may play an important role in promoting tumor growth [19].
• Cholecystokinin-1 receptor protein up-regulation during pancreatic regeneration after acute haemorrhagic pancreatitis in rats [1].

Anatomical context of Cckar

• Photoaffinity labeling using pancreatic membranes or acini demonstrated that 125I-ASA-JMV-179 detected a new 47-50-kDa protein in addition to the 85-100-kDa CCK-AR [18].
• However, the relative expression of the CCK-A receptor mRNA in DSL-6 pancreatic carcinoma was approximately 8-fold of that in normal rat pancreas [19].
• While CCK-AR is known to be expressed in rat islet B cells, the localization of CCK-AR in rat pancreatic A and D cells remains poorly understood [20].
• Structure-activity function for binding and signaling in CHO-K1 and COS-7 cells expressing the cholecystokinin A receptor [21].
• The intensity of CCKAR expression increased in nonvacuolated acinar cells; a decrease in the size of CCK-positive epithelial cells occurred in duodenum [22].

Associations of Cckar with chemical compounds

• The cDNA sequence encodes a 452-amino acid protein that is 48% identical to the CCKA receptor and contains seven transmembrane domains characteristics of guanine nucleotide-binding regulatory protein-coupled receptors [23].
• None of the three known phases of the febrile response of rats to LPS requires the CCK-A receptor [24].
• Overexpression of messenger RNA for cholecystokinin-A receptor and novel expression of messenger RNA for gastrin (cholecystokinin-B) receptor in azaserine-induced rat pancreatic carcinoma [19].
• Thus, devazepide, a selective CCK-A receptor antagonist, produced a dose-related inhibition of the CCK-8-stimulated rise in circulating beta-endorphin concentrations [25].
• CCK-8-evoked cationic current was antagonized by lorglumide, a selective CCK-A receptor antagonist [26].

Physical interactions of Cckar

• 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 [21].
• In conclusion, our results demonstrate CCKA receptor activation causes rapid tyrosine phosphorylation of p130(Cas) through PLC-dependent and -independent mechanisms that require the participation of the small GTP-binding protein Rho and the integrity of the actin cytoskeleton, but not the microtubule network [27].
• The high-affinity CCK-AR appears to be coupled to the Gbeta/cPLA2/arachidonic acid (AA) cascade in mediating Ca2+ oscillations [28].
• The low-affinity CCK-AR is coupled to both the Galphaq/11/PLCbeta1/inositol 1,4,5-trisphosphate (IP3) to evoke intracellular Ca2+ release and the Src/PTK pathway to mediate extracellular Ca2+ influx [28].

Regulatory relationships of Cckar

• 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 [29].
• 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 [30].
• These results indicate that CCK-8 stimulates pepsinogen secretion via CCK-2 receptors in CCK-1 receptor deficient OLETF rats and that the higher CCK-8-stimulated as well as basal pepsinogen secretion in OLETF rats might result from an elimination of tonic inhibition by somatostatin that is released from D cells through mainly CCK-1 receptors [31].
• In contrast, all three stimuli are known to increase PLD activity readily in Chinese hamster ovary (CHO) cells expressing the rat pancreatic acinar cell CCKA receptor [32].
• The specific gastrin antagonist L-365,260 inhibited the (partial) agonist activity of PD-136,450 in the stomach and the specific CCK-A receptor antagonist L-364,718 inhibited the agonist activity of PD-136,450 in the pancreas [33].

Other interactions of Cckar

• 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 [18].
• 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) [34].
• Increase in CYP1A1 and decrease in CCKAR expressions in vacuolated acinar cells may be involved in the pathogenesis of pancreatic lesions [22].
• Also in the latter, in the vacuolated acinar cells, CYP1A1 was overexpressed, and statistically significant decreases in expressions of AhR, CCKAR, and amylase occurred [22].
• Devazepide (3 mg x kg(-1)), a selective CCKA receptor antagonist, effectively attenuated the OT-induced inhibition of gastric emptying [35].

Analytical, diagnostic and therapeutic context of Cckar

• Further to this, immunofluorecsence staining using anti-glucagon antibody was carried out after in situ hybridization using the CCK-AR cRNA probe in order to identify CCK-AR mRNA expressing cells [20].
• Pancreatic CCK-1R protein was evaluated by immunoblot analysis and immunohistochemistry with a polyclonal antibody against rat CCK-1R protein [1].
• Pancreatic CCK-1R mRNA was determined by Northern blot analysis [1].
• 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 [36].
• Pretreatment with the CCK-A receptor antagonist, lorglumide (1 microM), antagonized the effects of CCK-8s, whereas perfusion with the CCK-B preferring agonist CCK-8 nonsulfated (CCK-ns, 1 microM) did not affect the frequency of sEPSCs [37].

References