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Heart rate responses to i.v. administration of cholecystokinin-8 (CCK-8) were investigated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats lacking CCK-A receptors and control Long-Evans Tokushima Otsuka (LETO) rats. The heart rate decreased after i.v. administration of 3 nmol.kg -1 of CCK-8 in LETO rats, but not in OLETF rats. Bradycardia in the LETO rats disappeared after treatment...
Cholecystokinin (CCK) is a neuropeptide expressed in the small intestine and in the central and peripheral nervous system. CCK gene expression is both spatially and temporally regulated. In neurons CCK production is increased by growth factors, cyclic adenosine 3', 5'-monophosphate (cAMP), dopamine, estrogen, and injury situations, while intestinal CCK expression is mainly regulated by food intake...
Serotonin 5-HT 3 antagonists have been suggested for treatment of several disorders involving altered gastrointestinal (GI) function. CCK also has well documented GI actions on both food intake and vago-vagal reflexes. To evaluate potential interactions, the effect of a 5-HT 3 antagonist, ondansetron, on exogenous CCK induced satiety and c-fos activation was determined. Ondansetron...
This study examined the effects of i.v. administration of cholecystokinin-tetrapeptide (CCK-4) on plasma release of arginine vasopressin (AVP) and oxytocin (OT) in women with premenstrual dysphoric disorder (PMDD) and control women, during both the follicular phase and the luteal phase of their menstrual cycle. Plasma AVP and OT concentrations increased following CCK-4 administration. AVP and OT response...
This review focuses on the interaction of estrogen with the cholecystokinin (CCK) and endogenous opioid peptide systems in the medial preoptic nucleus, and how these interactions result in alterations of a stereotypic female reproductive behavior-lordosis. The medial preoptic nucleus is an integral part of a circuit controlling lordosis that extends from the limbic system through the hypothalamus...
Previous studies have shown that sulfated cholecystokinin octapeptide (CCK-8S) can improve learning in adult rodents when administered systemically or into the central nucleus of amygdala. Here we analyzed the effect of repeated intraperitoneal (i.p.) injection of CCK-8S on the performance of 26-month-old Fischer 344 rats in different versions of the Morris water maze and in a rota-rod test of motor...
Insights into the molecular basis of binding of the peptide hormone, cholecystokinin, to its G protein-coupled receptor is of substantial interest and may contribute to the successful production and refinement of receptor-active drugs. A number of methodological approaches provide complementary data to contribute to these insights. These include receptor mutagenesis, ligand structure-activity data,...
The present review of the satiating effect of cholecystokinin in humans has revealed that cholecystokinin is a physiological satiety factor in humans. The results demonstrate the efficacy of the satiating actions of exogenous and endogenous CCK in humans. The therapeutic potential of CCK analogues cannot be estimated until further studies are performed that demonstrate the efficacy of CCK analogues...
The present article reviews our recent biochemical and microdialysis studies showing the evidence for an antagonistic CCK B /D 2 receptor interaction in the regulation of dopaminergic transmission in the nucleus accumbens and GABAergic transmission in the ipsilateral ventral pallidum. Since the nucleus accumbens plays a crucial role in regulating the output from the limbic system and...
Stereotyped behavior can be induced by the dopamine agonist apomorphine or by the releasing agent amphetamine. Cholecystokinin influence on dopamine-mediated behaviors has been extensively studied but a real controversy remains. Our purpose was to further characterize the dopamine-cholecystokinin interaction in apomorphine- and amphetamine-induced stereotyped behavior using sulphated cholecystokinin...
We investigated the effects of a CCK-A receptor antagonist on the development of mother preference. Lambs received 2-NAP either at birth or 6, or 12 h later. Controls were given saline. When tested at 24 h of age, lambs receiving 2-NAP at birth or 6 h later did not display mother preference unlike controls and lambs which were given 2-NAP at 12 h. The effect of the antagonist persisted at 48 h of...
The role of Cholecystokinin (CCK), a gut hormone and neuropeptide, in early learning was examined. Pairing a novel odor (presented away from the nest) with exogenously administered CCK (0.25 & 0.5 μg/kg IP) has been shown to produce a conditioned-odor preference in infant rats (Weller, A.; Blass, E.M. Behav. Neurosci. 104:199-206; 1990). This suggests that CCK can act as a positive unconditioned...
This issue of Peptides was inspired by a gathering of CCK researchers at the first Neuronal Cholecsytokinin Gordon Conference. The papers in this issue reflect the diversity of CCK research and demonstrate how the field has matured. Reviews describe the regulation of CCK gene expression and CCK release, the nature of the hormone binding site of the CCK A receptor, interaction of CCK, dopamine and...
Cholecystokinin (CCK) is a physiological antagonist of opioid-mediated antinociception and may be involved in some chronic pain states where opioids have reduced effect. We have previously shown in a rat model of central neuropathic pain after spinal cord injury that blockade of CCK-B receptors lead to marked pain relief. In the present study, we showed that spinally injured rats exhibiting chronic...
Thermoregulatory effects of cholecystokinin (CCK) peptides are reviewed with special emphasis on two types of responses, that is hypothermia or hyperthermia. In rodents exposed to cold a dose-dependent hypothermia has been observed on peripheral injection of CCK probably acting on CCKA receptors. Central microinjection of CCK in rats induced a thermogenic response that could be attenuated by CCKB...
Cholecystokinin peptides (CCK) have been shown to antagonize many opioid-mediated effects. The present study was undertaken to determine whether peripheral injections of cholecystokinin sulphated octapeptide (CCK8), cholecystokinin tetrapeptide (CCK4), the CCK 1 (lorglumide) and the CCK 2 (PD-135,158 and LY-225910) receptor antagonists can influence a classic morphine excitatory effect,...
Endocrine tumor cells in culture and in vitro cleavage assays have shown that PC1 and PC2 are capable of processing pro-CCK into smaller, intermediate and final, bioactive forms. Similar studies have shown that PC5 has the ability to process a number of propeptides. Here, we use GT1-7 (mouse hypothalamic) and SK-N-MC and SK-N-SH (human neuroblastoma) tumor cell lines to study the ability of PC5 to...
The high abundance of the cholecystokinin octapeptide in various brain regions is expressed by involvement of this neuropeptide in diverse brain functions. This peptide is mostly, if not always, co-localized with classic transmitters in central nerve terminals. Since the functions of the coexisting transmitters are often different, differential regulation of their release is obvious. This differentiation...
OLETF (Otsuka Long-Evans Tokushima Fatty) lacking the CCK 1 (A) receptor have similar spontaneous activity and locomotor response (horizontal and vertical activity) in response to a single injection of cocaine as the wild type LETO (Long Evans Tokushima Otsuka) rats. In contrast, the OLETF rats display more stereotypy in response to the first dose of cocaine than the LETO rats. Tested at 7 and 14...
Estradiol has long been known to inhibit feeding in animals, but the mechanism(s) mediating its effects have not been clear. Demonstrations that estradiol's feeding effects are expressed as decreases in meal size coupled with the emerging concensus that cholecystokinin (CCK) released from the small intestines during meals is a physiological negative-feedback signal controlling meal size (i.e. satiation)...
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