The distribution of cholecystokinin immunoreactivity in the central nervous system of the rat as determined by radioimmunoassay

doi:10.1016/0006-8993(81)90031-7

Brain Research

Volume 212, Issue 1, 11 May 1981, Pages 51-57

https://doi.org/10.1016/0006-8993(81)90031-7 Get rights and content

Abstract

The regional distribution of cholecystokinin (CCK) in the rat brain was determined utilizing a radioimmunoassay which detects both gastrin and CCK. CCK concentration is highest in the caudate nucleus (10–14 ng CCK8 equivalents/mg protein), followed by the cerebral cortex. Within the cerebral cortex, CCK is highest in the cingulate, pyriform, and entorhinal areas. There are substantial CCK concentrations in all other brain regions except pons, medulla and cerebellum. CCK is widely distributed in the hypothalamus, where it is highest in the median eminence and ventromedial nucleus. Considerable CCK-like immunoreactivity is also present in the posterior lobe of the pituitary gland, but is not detectable in anterior and intermediate lobes.

Though the antisera used in this study cross-react with gastrin the dominant CCK-like material found in rat brain co-elutes with sulfated CCK8 and separates from gastrin on Sephadex G-25 and HPLC chromatography.

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Cited by (492)

Entorhinohippocampal cholecystokinin modulates spatial learning by facilitating neuroplasticity of hippocampal CA3-CA1 synapses
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The hippocampus is broadly impacted by neuromodulations. However, how neuropeptides shape the function of the hippocampus and the related spatial learning and memory remains unclear. Here, we discover the crucial role of cholecystokinin (CCK) in heterosynaptic neuromodulation from the medial entorhinal cortex (MEC) to the hippocampus. Systematic knockout of the CCK gene impairs CA3-CA1 LTP and space-related performance. The MEC provides most of the CCK-positive neurons projecting to the hippocampal region, which potentiates CA3-CA1 long-term plasticity heterosynaptically in a frequency- and NMDA receptor (NMDAR)-dependent manner. Selective inhibition of MEC CCKergic neurons or downregulation of their CCK mRNA levels also impairs CA3-CA1 LTP formation and animals’ performance in the water maze. This excitatory extrahippocampal projection releases CCK upon high-frequency excitation and is active during animal exploration. Our results reveal the critical role of entorhinal CCKergic projections in bridging intra- and extrahippocampal circuitry at electrophysiological and behavioral levels.
Altered neurotransmission in stress-induced depressive disorders: The underlying role of the amygdala in depression
2023, Neuropeptides
Depression is the second leading cause of disability in the world population, for which currently available pharmacological therapies either have poor efficacy or have some adverse effects. Accumulating evidence from clinical and preclinical studies demonstrates that the amygdala is critically implicated in depressive disorders, though the underlying pathogenesis mechanism needs further investigation. In this literature review, we overviewed depression and the key role of Gamma-aminobutyric acid (GABA) and Glutamate neurotransmission in depression. Notably, we discussed a new cholecystokinin-dependent plastic changes mechanism under stress and a possible antidepressant response of cholecystokinin B receptor (CCKBR) antagonist. Moreover, we discussed the fundamental role of the amygdala in depression, to discuss and understand the pathophysiology of depression and the inclusive role of the amygdala in this devastating disorder.
Prohormone convertase 7 is necessary for the normal processing of cholecystokinin in mouse brain
2017, Biochemical and Biophysical Research Communications
Citation Excerpt :
Tissue samples were sonicated in ice cold 0.1 N HCL with an aliquot removed for the protein assay using the Bradford method [47]. CCK levels in the supernatants were measured using RIA [6]. The CCK antiserum used for measuring CCK cross-reacts equally well with different molecular forms of CCK and gastrin which have the carboxyl-terminal amide.
Endoproteases in the secretory pathway process pro-cholecystokinin (CCK) into the biologically active forms found in the tissues that express CCK mRNA. Thus far, the endoproteases involved in CCK processing include cathepsin L and the prohormone convertases (PC) 1, 2, and 5. This study finds that PC7 is also critical for normal production of CCK in specific areas of the brain. Loss of PC7 results in decreased levels of CCK in more brain regions than any other endoprotease studied to date. Substantial decreases in brain levels of CCK are found in the prefrontal, frontal, parietal-insular-pyriform, and temporal cortex, caudate-putamen, basal forebrain, thalamus, hippocampus, septum, and medulla of PC7 knock-out (KO) mice. A tissue-specific sexual dimorphism of PC7 activity was also identified. This is the first report that loss of PC7 alters levels of a neuropeptide in the brain. This loss of PC7 and CCK may independently contribute to the decrease in Brain Derived Neurotrophic Factor production and be partially responsible for the learning and memory defects observed in mice that lack PC7.
Aspergillus in Biomedical Research
2016, New and Future Developments in Microbial Biotechnology and Bioengineering: Aspergillus System Properties and Applications
With the advancements in availability of efficient tools and techniques of biochemistry, biotechnology, and molecular biology, the isolation, screening, and analysis of biological extracts has achieved immense progress. Since, the beginnings of human civilization fungi were used for making bread, beverages, and even for extracting poisonous compounds. The discoveries of antimicrobial compounds from fungi starting in the 1920s have further intensified their study. At present the therapeutic compounds isolated from fungi are countless and still continuing when compared with other groups of organisms. In addition, owing to the development of more sophisticated tools and methods, and in-depth knowledge of fungal ecology and genome sequencing data, the direction of drug discovery and research using fungi has stepped into isolation of many compounds useful for ameliorating and curing many genetics, physiological and metabolic diseases such as Alzheimer disease, diabetics, hypercholesterolemia, etc. Among the members of fungi, no other genus has been as widely explored and studied as Aspergillus for its applications in varied types of industries, such as foods, detergents, textiles, cosmetics, and pharmaceuticals. This chapter deals with the biomedical aspects of Aspergillus in order to provide further insight into the huge wealth of its usage as future sources and means for developing potent therapeutic compounds.
Exploring the association between a cholecystokinin promoter polymorphism (rs1799923) and posttraumatic stress disorder in combat veterans
2015, Journal of Anxiety Disorders
Citation Excerpt :
CCK is a common neuropeptide hormone present in a variety of forms (e.g. CCK-58, CCK-39, CCK-33, CCK-22, and CCK-8) that is derived from a 115-amino acid precursor molecule (Dockray, 1978; Deschenes et al., 1984; Harro, 2006). As one of the most abundant neuropeptides in the brain (Crawley, 1985; Moran & Schwartz, 1994), CCK performs important regulatory functions in both cortical and limbic areas (Beinfeld & Palkovits, 1982; Beinfeld, Meyer, Eskay, Jensen, & Brownstein, 1981) including in the amygdala (Beinfeld, 2001; Sherrin et al., 2009). The role of CCK in anxiety is well established (Bradwejn et al., 1992; Harro, Vasar, & Bradwejn, 1993; Rotzinger & Vaccarino, 2003), and biological challenge paradigms utilize the panicogenic effects of exogenous cholecystokinin tetrapeptide (CCK-4; the bioactive C-terminus of CCK peptides) to study processes underlying acute anxiety and panic within the laboratory (Rehfeld, 1992; DeMotigny, 1989; Rehfield, 2000).
Cholecystokinin (CCK) is a neuropeptide that has been implicated in understanding the acquisition and extinction of fear. Research on CCK in anxiety has primarily focused on understanding panic attacks and panic disorder. Emerging data suggests that CCK may also hold promise in understanding the development and maintenance of posttraumatic stress disorder (PTSD).
The present study examined whether a single nucleotide polymorphism in the promoter region of the CCK gene (C > T; rs1799923) was associated with an increased prevalence of PTSD as well as with severity of PTSD symptoms among a sample of 457 combat veterans.
Results demonstrated that participants with either the heterozygous or homozygous T allele had an increased prevalence of PTSD relative to participants with the CC genotype (OR = 2.17; 95% CI [1.37–3.43]).
The relatively small sample size precluded examination of racial/ethnic differences. Findings were also limited by the absence of a systematic assessment of comorbid anxiety psychopathology.
These data offer preliminary evidence supporting an association between the rs1799923 polymorphism in the CCK gene and PTSD. Additional research is needed to better understand the nature of this relationship.
Acute effects on brain cholecystokinin-like concentration and anxiety-like behaviour in the female rat upon a single injection of 17β-estradiol
2014, Pharmacology Biochemistry and Behavior
The neuropeptide cholecystokinin (CCK) has been implicated in the neurobiology of anxiety and panic disorders, as well as in dopamine-related behaviours. Anxiety and panic-disorders are twice as common in females compared to males, but studies of females are rare, although increasing in number. Limited studies have found that CCK fluctuates in limbic regions during the estrous cycle, and that CCK and its receptors are sensitive to estrogen.
The aim of the present work was to study the acute effects of 17β-estradiol on anxiety-like behaviour and on CCK-like immunoreactivity (LI) in the female rat brain (amygdala, hippocampus, nucleus accumbens, and cingulate cortex).
Four groups of female Sprague–Dawley rats were used: ovariectomized, ovariectomized + 17β-estradiol-replacement, sham, and sham + 17β-estradiol-replacement. The effect of 17β-estradiol-replacement on anxiety-related behaviour was measured in all animals on the elevated plus maze 2–24 h after injection. CCK-LI concentration was measured in punch biopsies by means of radioimmunoassay.
17β-estradiol decreased anxiety-like behaviour 2 h after administration in ovariectomized and sham-operated animals, as demonstrated by increased exploration of the open arms compared to respective sesame oil-treated controls. This effect was not present when testing occurred 24 h post-treatment. The rapid behavioural effect of 17β-estradiol was accompanied by changes in CCK-LI concentrations in regions of the limbic system including cingulate cortex, hippocampus, amygdala and nucleus accumbens.
Although the interpretation of these data requires caution since the data were collected from two different experiments, our results suggest that estrogen-induced anxiolytic effects may be associated with changes of the CCK-system in brain regions controlling anxiety-like behaviour.

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The distribution of cholecystokinin immunoreactivity in the central nervous system of the rat as determined by radioimmunoassay

Abstract

Brain Research

J. biol. Chem.

J. biol. Chem.

Evidence for the existence of monoamine containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons

Acta physiol. scand.

Isolation, structure and biological activity of two cholecystokinin octapeptides from sheep brain

Nature (Lond.)

Immunological and biologic properties of antibodies to a glucagon-serum albumin polymer

Endocrinology

Pancreozymin, a stimulant of the secretion of pancreatic enzymes in extracts of the small intestine

J. Physiol. (Lond.)

Cholecystokinin octapeptide-like immunoreactivity: histochemical localization in rat brain