Based on the experimental evidence from challenging the subject with a member of the cholecystokinin family, and on studies of the distribution of and binding to CCKreceptors, a conclusion may be drawn that the CCK system is involved in the regulation of anxiety and panic.
The investigation of CCK binding in the brains of suicide victims, who presumably experience stress and anxiety prior to the act, suggests an upregulation of binding in the frontal and cingulate cortex in comparison to matched controls (Harro et al., 1992).
An important part of the research on the implications of CCK peptides in the pathogenesis of panic attacks is the question whether antagonists of CCKreceptors would act as anxiolytics in the CCK-induced as well as in naturally occurring panic attacks.
"Development of Unified Models of CCKReceptor Subtypes" (PI, 1996-2001).
Abstract: The general goal of the present study is to use 3D models of the CCK-B and CCK-A peptide pharmacophores, previously obtained by comparison of a parent peptide and its peptide analogs, to design non-peptide agonists and antagonists presumably binding to the same sites of the CCK-B and CCK-Areceptors.
These studies will open the route to lead compounds, which could be developed to the level of pharmaceuticals.
CCKreceptor binding was studied in the receptor-expressing cells using the previously validated radioligand,
CCK competition-binding and CCK-stimulated biological activity curves for CHO cell line expressing cynomolgus type A CCKreceptor are shown.
Differences in partial agonist action at cholecystokinin receptors of mouse and rat are dependent on parameters extrinsic to receptor structure: molecular cloning, expression and functional characterization of the mouse type a cholecystokinin receptor.
CCK was obtained from Bachem (King of Prussia, PA).
CCK alone reduced current to 78 ± 1.6% of its initial value, whereas it was ineffective in the presence of either proglumide (Prog) or lorglumide (Lorg) (99 ± 2 or 97 ± 3.5%, respectively).
B, The number of cells responding to CCK in the presence of the PKA inhibitor H89 (13 of 25) is comparable with that responding to CCK alone (21 of 49), whereas CCK is almost ineffective as an inhibitor of potassium currents in the presence of the PKC inhibitor bisindolylmaleimide (3 of 18).
receptor gene amplification or rearrangement in pancreatic adenocarcinomas,
Povoski, and R.H. Bell (1993) Overexpression of messenger RNA for the cholecystokinin-A receptor and novel expression of messenger RNA for gastrin (cholecystokinin-B) receptor in azaserine induced rat pancreatic carcinoma.
Bell (1994) Cholecystokinin receptor characterization and cholecystokinin-A receptor mRNA expression in transgenic mouse pancreatic carcinomas and dysplastic pancreas.
Shown are representative emission curves for COS cells transfected with tagged CCKreceptor constructs separately or together as indicated.
A, shown are representative confocal microscopic images depicting type B CCKreceptor internalization in cells expressing this receptor alone or in the presence of type A CCKreceptor.
CHO cells stably expressing CCKreceptors were seeded 24 h before treatment and then changed to serum-free medium with or without G-17 or CCK.
The absence of gastrin/CCK-B receptors from most colorectal carcinoma specimens (table 2) and from colorectal carcinoma cell lines suggests that class I loops are infrequent.
Proglumide, a gastrin receptor antagonist, inhibits growth of colon cancer and enhances survival in mice.
The effect of the gastrin receptor antagonist proglumide on survival in gastric carcinoma.
Mediates these physiological effects by its endocrine actions in the intestines and by its paracrine and neurocrine actions in other parts of the body especially the brain.
CCK (1-8) is the most predominant form of the peptide in the brain and it exists as a sulphated (active) form (1-8S) and a desulphated (inactive) form.
Cholecystokinin acts by binding to the CCKreceptors (CCKr).
CCK was determined in both the culture medium (A) and the STC-1 cells (B) after a 1-h incubation with murine leptin or bombesin.
to be the soluble leptin receptor in the blood (26).
CCK, cholecystokinin; ERK, extracellular signal–related kinase; ERK-P, phospho-ERK; INSERM, the Institut National de la Santé et de la Recherche Médicale; IR, immunoreactive; MAPK, mitogen-activated protein kinase; MEK, MAPK kinase; PI3-K, phosphoinositide 3-kinase; RIA, radioimmunoassay; STAT, signal transducers and activators of transcription.
CCKreceptor subtype is involved for selection of the proper
receptor antibodies established by indirect immunofluorescence or confocal microscopy.
Rooman I, Lardon J, Flamez D, Schuit F, Bouwens L (2001) Mitogenic effect of gastrin and expression of gastrin receptors in duct-like cells of rat pancreas.
of receptor endocytosis in the absence of ligand-induced secondary
Matsumoto M, Park J, Yamada T (1987) Gastrin receptor characterization: affinity cross-linking of the gastrin receptor on canine gastric parietal cells.
Demonstration of the importance of the carboxyl terminus for ligand-induced internalization of the rat cholecystokinin type B receptor but not the type A receptor.
An Antiapoptotic Role for Gastrin and the Gastrin/CCK-2 Receptor in Barrett's Esophagus -- Harris et al.
Gastrin-cholecystokinin(B) receptor expression in AGS cells is associated with direct inhibition and indirect stimulation of cell proliferation via paracrine activation of the epidermal growth factor receptor.
Evidence for involvement of ERK5 kinase and transactivation of the epidermal growth factor receptor.
