cholecystokinin a receptor


Summary: A subtype of cholecystokinin receptor found primarily in the PANCREAS; STOMACH; INTESTINE; and GALLBLADDER. It plays a role in regulating digestive functions such as gallbladder contraction, pancreatic enzyme secretion and absorption in the GASTROINTESTINAL TRACT.

Top Publications

  1. Tsujino N, Yamanaka A, Ichiki K, Muraki Y, Kilduff T, Yagami K, et al. Cholecystokinin activates orexin/hypocretin neurons through the cholecystokinin A receptor. J Neurosci. 2005;25:7459-69 pubmed
    ..The evidence presented here expands our understanding of the regulation of orexin neurons and the physiological role of CCK in the CNS. ..
  2. Miyasaka K, Takata Y, Funakoshi A. Association of cholecystokinin A receptor gene polymorphism with cholelithiasis and the molecular mechanisms of this polymorphism. J Gastroenterol. 2002;37 Suppl 14:102-6 pubmed
    ..The genetic variations of cholecystokinin A receptor (CCK-AR) in patients having gallstones and the molecular mechanisms of this polymorhpism were examined...
  3. Lodge D, Lawrence A. Comparative analysis of the central CCK system in Fawn Hooded and Wistar Kyoto rats: extended localisation of CCK-A receptors throughout the rat brain using a novel radioligand. Regul Pept. 2001;99:191-201 pubmed
  4. Pellegrini M, Mierke D. Molecular complex of cholecystokinin-8 and N-terminus of the cholecystokinin A receptor by NMR spectroscopy. Biochemistry. 1999;38:14775-83 pubmed
    ..This mode of ligand binding, consistent with published mutagenesis studies, requires variation of the interpretation of recent findings from photoaffinity cross-linking studies. ..
  5. Glatzle J, Wang Y, Adelson D, Kalogeris T, Zittel T, Tso P, et al. Chylomicron components activate duodenal vagal afferents via a cholecystokinin A receptor-mediated pathway to inhibit gastric motor function in the rat. J Physiol. 2003;550:657-64 pubmed
  6. Minato T, Tochigi M, Kato N, Sasaki T. Association study between the cholecystokinin A receptor gene and schizophrenia in the Japanese population. Psychiatr Genet. 2007;17:117-9 pubmed
    b>Cholecystokinin A receptor (CCK-AR) has been implicated in the pathophysiology of schizophrenia through its mediation of dopamine-release in the central nervous system...
  7. Broberger C, Holmberg K, Shi T, Dockray G, Hokfelt T. Expression and regulation of cholecystokinin and cholecystokinin receptors in rat nodose and dorsal root ganglia. Brain Res. 2001;903:128-40 pubmed
    ..The stimulation of CCK and CCK(B)-R gene expression following vagotomy suggests a possible involvement in the response to injury for these molecules. ..
  8. Broberger C, Holmberg K, Kuhar M, Hokfelt T. Cocaine- and amphetamine-regulated transcript in the rat vagus nerve: A putative mediator of cholecystokinin-induced satiety. Proc Natl Acad Sci U S A. 1999;96:13506-11 pubmed
    ..A large proportion of CART-labeled neuron profiles also expressed cholecystokinin A receptor mRNA...
  9. Cowles R, Segura B, Mulholland M. Stimulation of rat pancreatic exocrine secretion by cocaine- and amphetamine-regulated transcript peptide. Regul Pept. 2001;99:61-8 pubmed
    ..CART peptide likely acts upon either peripheral or central regulators of pancreatic secretory function that are distant from the acinar unit. ..

More Information


  1. Gomez L, Hack M, McClure K, Sehon C, Huang L, Morton M, et al. SAR studies of 1,5-diarylpyrazole-based CCK1 receptor antagonists. Bioorg Med Chem Lett. 2007;17:6493-8 pubmed
    ..The difference in affinity between the two enantiomers for the CCK(1) receptor and the flexible nature of the linker led to the design of constrained analogs with increased potency. ..
  2. Miyasaka K, Kobayashi S, Ohta M, Kanai S, Yoshida Y, Nagata A, et al. Anxiety-related behaviors in cholecystokinin-A, B, and AB receptor gene knockout mice in the plus-maze. Neurosci Lett. 2002;335:115-8 pubmed
    ..We therefore conclude that a lack of CCK-BR increases the anxiety-related behavior of the mouse in the elevated plus- maze. ..
  3. Hernandez Gómez A, Aguilar Roblero R, Perez de la Mora M. Role of cholecystokinin-A and cholecystokinin-B receptors in anxiety. Amino Acids. 2002;23:283-90 pubmed
    ..Finally, CCK-33 injected into the postero-medial nucleus accumbens failed to affect the anxiety level of the rats. These results indicate that CCKA receptors are not involved in anxiety, as measured by the paradigms used in this work. ..
  4. Hayes M, Savastano D, Covasa M. Cholecystokinin-induced satiety is mediated through interdependent cooperation of CCK-A and 5-HT3 receptors. Physiol Behav. 2004;82:663-9 pubmed
    ..Most likely, this interconnection exists through a feed-forward parallel model arising from CCK-A and 5-HT3 receptors, where activation of one system engages the other to intensify the overall satiety signal. ..
  5. Felix F, Fontenele J. The OLETF rat as a model of central sensitization: possible relevance to the study of fibromyalgia and related diseases. J Pharmacol Sci. 2007;105:372 pubmed
  6. Allison B, Phuong V, McAtee L, Rosen M, Morton M, Prendergast C, et al. Identification and optimization of anthranilic sulfonamides as novel, selective cholecystokinin-2 receptor antagonists. J Med Chem. 2006;49:6371-90 pubmed
  7. Sato N, Miyasaka K, Suzuki S, Kanai S, Ohta M, Kawanami T, et al. Lack of cholecystokinin-A receptor enhanced gallstone formation: a study in CCK-A receptor gene knockout mice. Dig Dis Sci. 2003;48:1944-7 pubmed
    ..Sludge and gallstone formation were not observed at 6 months of age. In conclusion, deteriorated gallbladder contraction due to a lack of CCK-AR favored gallstone formation after the middle age of life. ..
  8. Takahashi M, Naito H, Sasaki I, Funayama Y, Shibata C, Matsuno S. Long-term bile diversion enhances basal and duodenal oleate-stimulated pancreatic exocrine secretion in dogs. Tohoku J Exp Med. 2004;203:87-95 pubmed
    ..Long-term bile diversion enhances basal and oleate-stimulated pancreatic exocrine secretion, at least partly via increased cholecystokinin secretion. ..
  9. Matsushita H, Akiyoshi J, Kai K, Ishii N, Kodama K, Tsutsumi T, et al. Spatial memory impairment in OLETF rats without cholecystokinin - a receptor. Neuropeptides. 2003;37:271-6 pubmed
    ..In PA, OLETF rats did not show facilitating response 24 h after training. From these observations, we concluded that a spatial memory was impaired in the OLETF rats...
  10. Sartor D, Verberne A. Cholecystokinin selectively affects presympathetic vasomotor neurons and sympathetic vasomotor outflow. Am J Physiol Regul Integr Comp Physiol. 2002;282:R1174-84 pubmed
    ..RVLM neurons inhibited by exogenous CCK acting via CCK-A receptors on vagal afferents may control sympathetic vasomotor outflow to the gastrointestinal tract vasculature. ..
  11. Lin H, Zaidel O, Hum S. Intestinal transit of fat depends on accelerating effect of cholecystokinin and slowing effect of an opioid pathway. Dig Dis Sci. 2002;47:2217-21 pubmed
    ..05) of naloxone occurred later. We conclude that fat-induced jejunal brake depends on the early accelerating effect of CCK and the later slowing effect of a naloxone-sensitive opioid pathway. ..
  12. Latorre M, Bartolomé Nebreda J, Garcia Lopez M, González Muñiz R, Herranz R, Del Rio J, et al. Pharmacological study of IQM-97,423, a potent and selective CCK1 receptor antagonist with protective effect in experimental acute pancreatitis. Pharmacology. 2004;72:68-76 pubmed
    ..Consequently, the pyridopyrimidine derivative IQM-97,423 is a potent and highly selective CCK1 receptor antagonist with preventive effects in two experimental models of acute pancreatitis and a potential therapeutic interest. ..
  13. Jang J, Kim S, Ku J, Park Y, Park J. Presence of CCK-A, B receptors and effect of gastrin and cholecystokinin on growth of pancreatobiliary cancer cell lines. World J Gastroenterol. 2005;11:803-9 pubmed
    ..Gastrin and CCK exert a trophic action on some of the biliary tract cancers. ..
  14. Yang Y, Chung J, Rhim H. Cellular action of cholecystokinin-8S-mediated excitatory effects in the rat periaqueductal gray. Life Sci. 2006;79:1702-11 pubmed
    ..These effects may be important for the effects of CCK on behavior and autonomic function that are mediated via PAG neurons. ..
  15. Cawston E, Miller L. Therapeutic potential for novel drugs targeting the type 1 cholecystokinin receptor. Br J Pharmacol. 2010;159:1009-21 pubmed publisher
    ..The case is built for the potential importance of developing more selective partial agonists and allosteric modulators of this receptor that could have important roles in the treatment of common clinical syndromes. ..
  16. Bi S, Moran T. Actions of CCK in the controls of food intake and body weight: lessons from the CCK-A receptor deficient OLETF rat. Neuropeptides. 2002;36:171-81 pubmed
    ..Thus, the obesity in the OLETF rats may be the outcome of two regulatory disruptions, one depending upon a peripheral within meal satiety pathway and the other depending upon a central pathway critical to overall energy balance. ..
  17. Whited K, Hornof W, Garcia T, Bohan D, Larson R, Raybould H. A non-invasive method for measurement of gastric emptying in mice: effects of altering fat content and CCK A receptor blockade. Neurogastroenterol Motil. 2004;16:421-7 pubmed
    ..These results demonstrate the sensitivity and predictability of this technique in mice and importantly, provide an opportunity to alter the macronutrient or caloric content of the meal to determine effects on gastric emptying. ..
  18. Glatzle J, Darcel N, Rechs A, Kalogeris T, Tso P, Raybould H. Apolipoprotein A-IV stimulates duodenal vagal afferent activity to inhibit gastric motility via a CCK1 pathway. Am J Physiol Regul Integr Comp Physiol. 2004;287:R354-9 pubmed
  19. Corsi M, Palea S, Pietra C, Oliosi B, Gaviraghi G, Sugg E, et al. A further analysis of the contraction induced by activation of cholecystokinin A receptors in guinea pig isolated ileum longitudinal muscle-myenteric plexus. J Pharmacol Exp Ther. 1994;270:734-40 pubmed
    ..In the presence of atropine and GR 82334, both 300 nM, a synergistic depression of the response to senktide similar to that observed for the agonist NAA was disclosed.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  20. Wu V, Yang M, McRoberts J, Ren J, Seensalu R, Zeng N, et al. First intracellular loop of the human cholecystokinin-A receptor is essential for cyclic AMP signaling in transfected HEK-293 cells. J Biol Chem. 1997;272:9037-42 pubmed
    ..5 +/- 1 nM and 23 +/- 7 nM, respectively. These data suggest that the first intracellular loop of CCK-AR is essential for coupling to Gs and activation of adenylyl cyclase signal transduction cascade. ..
  21. Roses A. Stimulation of cholecystokinin-A receptors with Gl181771X: a failed clinical trial that did not test the pharmacogenetic hypothesis for reduction of food intake. Clin Pharmacol Ther. 2009;85:362-5 pubmed publisher
    ..The hypotheses should have been based on the original putative role of a central mechanism affecting appetite, which had been validated using efficacy PGx in phase IIA. ..
  22. West S, Helmer K, Chang L, Cui Y, Greeley G, Mercer D. Cholecystokinin secretagogue-induced gastroprotection: role of nitric oxide and blood flow. Am J Physiol Gastrointest Liver Physiol. 2003;284:G399-410 pubmed
    ..The protective mechanism appears to involve increased production of nitric oxide from primarily the constitutive isoforms of NOS and a resultant increase in blood flow. ..
  23. Takata Y, Takeda S, Kawanami T, Takiguchi S, Yoshida Y, Miyasaka K, et al. Promoter analysis of human cholecystokinin type-A receptor gene. J Gastroenterol. 2002;37:815-20 pubmed
    ..However, no significant differences were found for the promoter activities of polymorphic promoter constructs. Conclusions. These results suggest that the reported polymorphism may not play a role in transcriptional regulation. ..
  24. Rooman I, Lardon J, Flamez D, Schuit F, Bouwens L. Mitogenic effect of gastrin and expression of gastrin receptors in duct-like cells of rat pancreas. Gastroenterology. 2001;121:940-9 pubmed
    ..Duct-like pancreatic epithelial cells in vitro and ductal complexes in vivo express gastrin/CCK-B receptors and proliferate in response to gastrin. ..
  25. Tarasova N, Stauber R, Choi J, Hudson E, Czerwinski G, Miller J, et al. Visualization of G protein-coupled receptor trafficking with the aid of the green fluorescent protein. Endocytosis and recycling of cholecystokinin receptor type A. J Biol Chem. 1997;272:14817-24 pubmed
  26. Gautron L, Lee C, Funahashi H, Friedman J, Lee S, Elmquist J. Melanocortin-4 receptor expression in a vago-vagal circuitry involved in postprandial functions. J Comp Neurol. 2010;518:6-24 pubmed publisher
  27. Dunlop J, Zhang Y, Evans N. Full and partial agonist activity of C-terminal cholecystokinin peptides at the cloned human CCK-A receptor expressed in Chinese hamster ovary cells. Peptides. 1997;18:865-8 pubmed
    ..These results demonstrate that CCK-8S represents the minimum ligand requirement for both high affinity and full agonist activity at the human CCK-A receptor subtype. ..
  28. Storr M, Sattler D, Hahn A, Schusdziarra V, Allescher H. Endogenous CCK depresses contractile activity within the ascending myenteric reflex pathway of rat ileum. Neuropharmacology. 2003;44:524-32 pubmed
    ..Thus in experiments investigating more complex neuronal circuits, experiments with antagonists should be regarded as more specific. ..
  29. Tachikawa H, Harada S, Kawanishi Y, Okubo T, Suzuki T. Linked polymorphisms (-333G>T and -286A>G) in the promoter region of the CCK-A receptor gene may be associated with schizophrenia. Psychiatry Res. 2001;103:147-55 pubmed
    ..The results supported our previous data, and suggest the possible involvement of the -333G>T and the -286A>G polymorphisms in the promoter region of the CCKAR gene in the predisposition to schizophrenia. ..
  30. Blevins J, Overduin J, Fuller J, Cummings D, Matsumoto K, Moralejo D. Normal feeding and body weight in Fischer 344 rats lacking the cholecystokinin-1 receptor gene. Brain Res. 2009;1255:98-112 pubmed publisher
  31. Maletinska L, Maixnerová J, Matysková R, Haugvicova R, Pirnik Z, Kiss A, et al. Synergistic effect of CART (cocaine- and amphetamine-regulated transcript) peptide and cholecystokinin on food intake regulation in lean mice. BMC Neurosci. 2008;9:101 pubmed publisher
  32. Shimokata H, Ando F, Niino N, Miyasaka K, Funakoshi A. Cholecystokinin A receptor gene promoter polymorphism and intelligence. Ann Epidemiol. 2005;15:196-201 pubmed
    To study the association between Cholecystokinin A receptor (CCKAR) genotypes and intelligence in community-living men and women. Subjects were 2251 community-dwelling Japanese men and women aged 40 to 79 years...
  33. Ivanov A, Kulchitsky V, Romanovsky A. Role for the cholecystokinin-A receptor in fever: a study of a mutant rat strain and a pharmacological analysis. J Physiol. 2003;547:941-9 pubmed
    ..None of the three known phases of the febrile response of rats to LPS requires the CCK-A receptor. ..
  34. Reeve J, McVey D, Bunnett N, Solomon T, Keire D, Ho F, et al. Differences in receptor binding and stability to enzymatic digestion between CCK-8 and CCK-58. Pancreas. 2002;25:e50-5 pubmed
    ..The results strongly support the hypothesis that differences in tertiary structure of the carboxyl terminus of CCK-8 and CCK-58 influence receptor binding and stability to enzymatic digestion. ..
  35. Miyasaka K, Yoshida Y, Matsushita S, Higuchi S, Maruyama K, Niino N, et al. Association of cholecystokinin-A receptor gene polymorphism with alcohol dependence in a Japanese population. Alcohol Alcohol. 2004;39:25-8 pubmed
    ..In addition, the age of onset of alcohol dependence was significantly earlier in patients with this allele. The CCK-AR gene -81A/G polymorphism, especially in the -81G allele, may be associated with intractable alcoholism. ..
  36. Proschowsky H, Fredholm M. Exocrine pancreatic insufficiency in the Eurasian dog breed--inheritance and exclusion of two candidate genes. Anim Genet. 2007;38:171-3 pubmed
    ..Based on our results, we excluded the canine orthologs of the human cholecystokinin (CCK) and the cholecystokinin A receptor (CCKAR) genes as candidates for exocrine pancreatic insufficiency.
  37. Nawrot Porabka K, Jaworek J, Leja Szpak A, Szklarczyk J, Kot M, Mitis Musioł M, et al. Involvement of vagal nerves in the pancreatostimulatory effects of luminal melatonin, or its precursor L-tryptophan. Study in the rats. J Physiol Pharmacol. 2007;58 Suppl 6:81-95 pubmed
    ..We conclude that melatonin as well as its precursor L-tryptophan, stimulates pancreatic exocrine function via mechanisms involving enteropancreatic reflexes and CCK. ..
  38. Morton M, Barrett T, Yan W, Freedman J, Lagaud G, Prendergast C, et al. 3-[5-(3,4-Dichloro-phenyl)-1-(4-methoxy-phenyl)-1H-pyrazol-3-yl]-2-m-tolyl-propionate (JNJ-17156516), a novel, potent, and selective cholecystokinin 1 receptor antagonist: in vitro and in vivo pharmacological comparison with dexloxiglumide. J Pharmacol Exp Ther. 2007;323:562-9 pubmed
    ..0 +/- 0.5 h and a very high bioavailability (108 +/- 10%) in this species. Overall, we have demonstrated that JNJ-17156516 is a high-affinity selective human CCK1 receptor antagonist with good pharmacokinetic properties in rats. ..
  39. De Luca S, Ragone R, Bracco C, Digilio G, Aloj L, Tesauro D, et al. A cyclic CCK8 analogue selective for the cholecystokinin type A receptor: design, synthesis, NMR structure and binding measurements. Chembiochem. 2003;4:1176-87 pubmed
    ..Preliminary nuclear medicine studies on cell lines transfected with the CCK(A) receptor indicate that the sulfated-Tyr derivative of cyclo(29,34)[Dpr(29),Lys(34)]-CCK8 displaces the natural ligand with an IC(50) value of 15 microM. ..
  40. Swartz T, Hajnal A, Covasa M. Altered orosensory sensitivity to oils in CCK-1 receptor deficient rats. Physiol Behav. 2010;99:109-17 pubmed publisher
    ..Collectively, these results show that increased oil intake in OLETF rats is driven by both peripheral deficits to satiation and altered orosensory sensitivity. ..
  41. Harikumar K, Miller L. Use of fluorescence indicators in receptor ligands. Methods Mol Biol. 2009;552:279-91 pubmed publisher
    ..These methods represent powerful tools to expand our understanding of the structure and function of G protein-coupled receptors. ..
  42. Varga G, Balint A, Burghardt B, D Amato M. Involvement of endogenous CCK and CCK1 receptors in colonic motor function. Br J Pharmacol. 2004;141:1275-84 pubmed
    ..These drugs are therefore potentially of great value in the treatment of motility disorders such as constipation and constipation-predominant IBS. ..
  43. Wu C, Hung C, Chang F, Lin L, Pau K, Wang P. Effects of evodiamine on gastrointestinal motility in male rats. Eur J Pharmacol. 2002;457:169-76 pubmed
    ..These results suggest that evodiamine inhibits both gastric emptying and gastrointestinal transit in male rats via a mechanism involving CCK release and CCK(1) receptor activation. ..
  44. Romanelli L, Amico M, Mattioli F, Morrone L, Valeri P. Interactions between cholecystokinin and opioids in the isolated guinea-pig ileum. Br J Pharmacol. 1999;127:909-18 pubmed
    ..5. These results show that CCK-8 preferentially activates the GPI kappa-opioid system and antagonizes the mechanism(s) that control the expression of acute dependence in the GPI. ..
  45. Sanjuan J. [The aetiopathogenesis of auditory hallucinations in psychosis]. Rev Neurol. 2006;43:280-6 pubmed
    ..Our model allow the integration of many data from epidemiology and neuroimaging, to psychopharmacology in the understanding of the aetiology of auditory hallucinations. ..
  46. Miyasaka K, Suzuki S, Kanai S, Masuda M, Funakoshi A. Role of CCK-A receptor in the regulation of pancreatic bicarbonate secretion in conscious rats: a study in naturally occurring CCK-A receptor gene knockout rats. Pancreas. 1999;19:217-23 pubmed
    ..In conclusion, intravenous injection of CCK did not stimulate bicarbonate secretion, and the lack of CCK-A receptor decreased bicarbonate secretion in response to luminal stimulants. ..
  47. Jaworek J, Nawrot Porabka K, Leja Szpak A, Szklarczyk J, Macko M, Bonior J, et al. Exposition of newborn rats to bacterial endotoxin impairs pancreatic enzyme secretion at adult age. J Physiol Pharmacol. 2007;58:287-302 pubmed
    ..We conclude that neonatal endotoxemia reduces gene expression for CCK1 receptor and could produce impairment of the exocrine pancreatic function at adult age. ..
  48. Holicky E, Hadac E, Ding X, Miller L. Molecular characterization and organ distribution of type A and B cholecystokinin receptors in cynomolgus monkey. Am J Physiol Gastrointest Liver Physiol. 2001;281:G507-14 pubmed
    ..This work confirms the relevance of the cynomolgus species for preclinical testing of drugs acting on the type A CCK receptor. ..
  49. Xiao Z, Schmitz F, Pricolo V, Biancani P, Behar J. Role of caveolae in the pathogenesis of cholesterol-induced gallbladder muscle hypomotility. Am J Physiol Gastrointest Liver Physiol. 2007;292:G1641-9 pubmed
  50. Hokfelt T, Holmberg K, Shi T, Broberger C. CCK-ergic mechanisms in sensory systems. Scand J Clin Lab Invest Suppl. 2001;234:69-74 pubmed
    ..In man and monkey the CCK1 receptor seems important in the dorsal horn under normal conditions, indicating distinct species differences. ..
  51. Giacobini P, Kopin A, Beart P, Mercer L, Fasolo A, Wray S. Cholecystokinin modulates migration of gonadotropin-releasing hormone-1 neurons. J Neurosci. 2004;24:4737-48 pubmed
  52. Guilmeau S, Nagain Domaine C, Buyse M, Tsocas A, Rozé C, Bado A. Modulation of exocrine pancreatic secretion by leptin through CCK(1)-receptors and afferent vagal fibres in the rat. Eur J Pharmacol. 2002;447:99-107 pubmed
    ..Whether this may have a physiological relevance in the postprandial regulation of exocrine pancreatic secretion and thus in nutrient digestion will require further investigations. ..
  53. Giragossian C, Stone S, Papini A, Moroder L, Mierke D. Conformational and molecular modeling studies of sulfated cholecystokinin-15. Biochem Biophys Res Commun. 2002;293:1053-9 pubmed