-
The Journal of Physiological Sciences :... Feb 2024Many hormones act on the hypothalamus to control hunger and satiety through various pathways closely associated with several factors. When food is present in the gastro... (Review)
Review
Many hormones act on the hypothalamus to control hunger and satiety through various pathways closely associated with several factors. When food is present in the gastro intestinal (GI) tract, enteroendocrine cells (EECs) emit satiety signals such as cholecystokinin (CCK), glucagon like peptide-1 (GLP-1) and peptide YY (PYY), which can then communicate with the vagus nerve to control food intake. More specifically, satiety has been shown to be particularly affected by the GLP-1 hormone and its receptor agonists that have lately been acknowledged as a promising way to reduce weight. In addition, there is increasing evidence that normal flora is also involved in the peripheral, central, and reward system that impact satiety. Moreover, neurologic pathways control satiety through neurotransmitters. In this review, we discuss the different roles of each of the GLP-1 hormone and its agonist, gut microbiomes, as well as neurotransmitters and their interconnected relation in the regulation of body's satiety homeostasis.
Topics: Cholecystokinin; Glucagon-Like Peptide 1; Peptide YY; Brain; Neurotransmitter Agents
PubMed: 38368346
DOI: 10.1186/s12576-024-00904-9 -
International Journal of Molecular... Dec 2021Opioids are the most potent widely used analgesics, primarily, but not exclusively, in palliative care. However, they are associated with numerous side effects, such as... (Review)
Review
Opioids are the most potent widely used analgesics, primarily, but not exclusively, in palliative care. However, they are associated with numerous side effects, such as tolerance, addiction, respiratory depression, and cardiovascular events. This, in turn, can result in their overuse in cases of addiction, the need for dose escalation in cases of developing tolerance, and the emergence of dose-related opioid toxicity, resulting in respiratory depression or cardiovascular problems that can even lead to unintentional death. Therefore, a very important challenge for researchers is to look for ways to counteract the side effects of opioids. The use of peptides and their related compounds, which have been shown to modulate the effects of opioids, may provide such an opportunity. This short review is a compendium of knowledge about the most important and recent findings regarding selected peptides and their modulatory effects on various opioid actions, including cardiovascular and respiratory responses. In addition to the peptides more commonly reported in the literature in the context of their pro- and/or anti-opioid activity-such as neuropeptide FF (NPFF), cholecystokinin (CCK), and melanocyte inhibiting factor (MIF)-we also included in the review nociceptin/orphanin (N/OFQ), ghrelin, oxytocin, endothelin, and venom peptides.
Topics: Analgesics, Opioid; Animals; Cholecystokinin; Drug Tolerance; Ghrelin; Humans; Narcotic Antagonists; Oligopeptides; Opioid Peptides; Peptides; Receptors, Opioid; Nociceptin
PubMed: 34948415
DOI: 10.3390/ijms222413619 -
Molecules (Basel, Switzerland) Sep 2021The classic gut hormone cholecystokinin (CCK) and its CCK-receptor are expressed in almost all regions of the brain. This widespread expression makes CCK by far the most... (Review)
Review
The classic gut hormone cholecystokinin (CCK) and its CCK-receptor are expressed in almost all regions of the brain. This widespread expression makes CCK by far the most abundant peptidergic transmitter system in the brain. This CNS-ubiquity has, however, complicated the delineation of the roles of CCK peptides in normal brain functions and neuropsychiatric diseases. Nevertheless, the common panic disorder disease is apparently associated with CCK in the brain. Thus, the C-terminal tetrapeptide fragment of CCK (CCK-4) induces, by intravenous administration in a dose-related manner, panic attacks that are similar to the endogenous attacks in panic disorder patients. This review describes the history behind the discovery of the panicogenic effect of CCK-4. Subsequently, the review discusses three unsettled questions about the involvement of cerebral CCK in the pathogenesis of anxiety and panic disorder, including therapeutic attempts with CCK-receptor antagonists.
Topics: Adult; Cholecystokinin; Humans; Panic Disorder
PubMed: 34577128
DOI: 10.3390/molecules26185657 -
Cell Reports Feb 2022Escape is an evolutionarily conserved and essential avoidance response. Considered to be innate, most studies on escape responses focused on hard-wired circuits. We...
Escape is an evolutionarily conserved and essential avoidance response. Considered to be innate, most studies on escape responses focused on hard-wired circuits. We report here that a neuropeptide NLP-18 and its cholecystokinin receptor CKR-1 enable the escape circuit to execute a full omega (Ω) turn. We demonstrate in vivo NLP-18 is mainly secreted by the gustatory sensory neuron (ASI) to activate CKR-1 in the head motor neuron (SMD) and the turn-initiating interneuron (AIB). Removal of NLP-18 or CKR-1 or specific knockdown of CKR-1 in SMD or AIB neurons leads to shallower turns, hence less robust escape steering. Consistently, elevation of head motor neuron (SMD)'s Ca transients during escape steering is attenuated upon the removal of NLP-18 or CKR-1. In vitro, synthetic NLP-18 directly evokes CKR-1-dependent currents in oocytes and CKR-1-dependent Ca transients in SMD. Thus, cholecystokinin peptidergic signaling modulates an escape circuit to generate robust escape steering.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cholecystokinin; Locomotion; Neuropeptides; Sensory Receptor Cells; Signal Transduction
PubMed: 35139370
DOI: 10.1016/j.celrep.2022.110330 -
American Journal of Physiology.... Jan 2014The gastrointestinal peptide cholecystokinin (CCK) causes the release of pancreatic digestive enzymes and growth of the normal pancreas. Exogenous CCK administration has... (Review)
Review
The gastrointestinal peptide cholecystokinin (CCK) causes the release of pancreatic digestive enzymes and growth of the normal pancreas. Exogenous CCK administration has been used in animal models to study pancreatitis and also as a promoter of carcinogen-induced or Kras-driven pancreatic cancer. Defining CCK receptors in normal human pancreas has been problematic because of its retroperitoneal location, high concentrations of pancreatic proteases, and endogenous RNase. Most studies indicate that the predominant receptor in human pancreas is the CCK-B type, and CCK-A is the predominant form in rodent pancreas. In pancreatic cancer cells and tumors, the role of CCK is better established because receptors are often overexpressed by these cancer cells and stimulation of such receptors promotes growth. Furthermore, in established cancer, endogenous production of CCK and/or gastrin occurs and their actions stimulate the synthesis of more receptors plus growth by an autocrine mechanism. Initially it was thought that the mechanism by which CCK served to potentiate carcinogenesis was by interplay with inflammation in the pancreatic microenvironment. But with the recent findings of CCK receptors on early PanIN (pancreatic intraepithelial neoplasia) lesions and on stellate cells, the question has been raised that perhaps CCK actions are not the result of cancer but an early driving promoter of cancer. This review will summarize what is known regarding CCK, its receptors, and pancreatic cancer, and also what is unknown and requires further investigation to determine which comes first, the chicken or the egg, "CCK or the cancer."
Topics: Animals; Cholecystokinin; Disease Progression; Humans; Mice; Pancreatic Neoplasms; Rats; Receptors, Cholecystokinin; Signal Transduction
PubMed: 24177032
DOI: 10.1152/ajpgi.00301.2013 -
ELife Aug 2022Animals must learn through experience which foods are nutritious and should be consumed, and which are toxic and should be avoided. Enteroendocrine cells (EECs) are the...
Animals must learn through experience which foods are nutritious and should be consumed, and which are toxic and should be avoided. Enteroendocrine cells (EECs) are the principal chemosensors in the GI tract, but investigation of their role in behavior has been limited by the difficulty of selectively targeting these cells in vivo. Here, we describe an intersectional genetic approach for manipulating EEC subtypes in behaving mice. We show that multiple EEC subtypes inhibit food intake but have different effects on learning. Conditioned flavor preference is driven by release of cholecystokinin whereas conditioned taste aversion is mediated by serotonin and substance P. These positive and negative valence signals are transmitted by vagal and spinal afferents, respectively. These findings establish a cellular basis for how chemosensing in the gut drives learning about food.
Topics: Animals; Cholecystokinin; Enteroendocrine Cells; Food; Food Preferences; Mice; Reward; Taste
PubMed: 35913117
DOI: 10.7554/eLife.74964 -
Nutrition (Burbank, Los Angeles County,... Oct 2000In the almost 30 years since the ability of peripheral administration of the brain/gut peptide cholecystokinin (CCK) to inhibit food intake was first demonstrated,... (Review)
Review
In the almost 30 years since the ability of peripheral administration of the brain/gut peptide cholecystokinin (CCK) to inhibit food intake was first demonstrated, significant progress in our overall understanding of the role of CCK in ingestive behavior has been made. A physiologic role for endogenous CCK in the control of meal size has been demonstrated and sites and mechanisms of action for CCK in food intake have been investigated. Recent work has uncovered roles for the CCK satiety pathway in the mediation of the feeding modulatory actions of estradiol, insulin, and leptin. The availability of the Otsuka Long Evans Tokushima Fatty (OLETF) rat, a strain lacking CCK(A) receptors, provides a unique model for the study of how deficits in a within-meals satiety signaling pathway may result in long-term changes in food intake and body weight.
Topics: Animals; Appetite Regulation; Cholecystokinin; Eating; Energy Metabolism; Humans; Hyperphagia; Models, Animal; Obesity; Rats; Rats, Inbred OLETF; Receptors, Cholecystokinin; Satiation
PubMed: 11054590
DOI: 10.1016/s0899-9007(00)00419-6 -
The Journal of Physiology Feb 2012Cortical neuronal network operations depend critically on the recruitment of GABAergic interneurons and the properties of their inhibitory output signals. Recent... (Review)
Review
Cortical neuronal network operations depend critically on the recruitment of GABAergic interneurons and the properties of their inhibitory output signals. Recent evidence indicates a marked difference in the signalling properties of two major types of perisomatic inhibitory interneurons, the parvalbumin- and the cholecystokinin-containing basket cells. Parvalbumin-expressing basket cells are rapidly recruited by excitatory synaptic inputs, generate high-frequency trains of action potentials, discharge single action potentials phase-locked to fast network oscillations and provide fast, stable and timed inhibitory output onto their target cells. In contrast, cholecystokinin-containing basket cells are recruited in a less reliable manner, discharge at moderate frequencies with single action potentials weakly coupled to the phases of fast network oscillations and generate an asynchronous, fluctuating and less timed inhibitory output. These signalling modes are based on cell type-dependent differences in the functional and plastic properties of excitatory input synapses, integrative qualities and in the kinetics and dynamics of inhibitory output synapses. Thus, the two perisomatic inhibitory interneuron types operate with different speed and precision and may therefore contribute differently to the operations of neuronal networks.
Topics: Animals; Cholecystokinin; Interneurons; Parvalbumins
PubMed: 22250212
DOI: 10.1113/jphysiol.2011.226175 -
Molecular Psychiatry Dec 2023Inhibitory interneurons are crucial to brain function and their dysfunction is implicated in neuropsychiatric conditions. Emerging evidence indicates that...
Inhibitory interneurons are crucial to brain function and their dysfunction is implicated in neuropsychiatric conditions. Emerging evidence indicates that cholecystokinin (CCK)-expressing interneurons (CCK+) are highly heterogenous. We find that a large subset of parvalbumin-expressing (PV+) interneurons express CCK strongly; between 40 and 56% of PV+ interneurons in mouse hippocampal CA1 express CCK. Primate interneurons also exhibit substantial PV/CCK co-expression. Mouse PV+/CCK+ and PV+/CCK- cells show distinguishable electrophysiological and molecular characteristics. Analysis of single nuclei RNA-seq and ATAC-seq data shows that PV+/CCK+ cells are a subset of PV+ cells, not of synuclein gamma positive (SNCG+) cells, and that they strongly express oxidative phosphorylation (OXPHOS) genes. We find that mitochondrial complex I and IV-associated OXPHOS gene expression is strongly correlated with CCK expression in PV+ interneurons at both the transcriptomic and protein levels. Both PV+ interneurons and dysregulation of OXPHOS processes are implicated in neuropsychiatric conditions, including autism spectrum (ASD) disorder and schizophrenia (SCZ). Analysis of human brain samples from patients with these conditions shows alterations in OXPHOS gene expression. Together these data reveal important molecular characteristics of PV-CCK co-expressing interneurons and support their implication in neuropsychiatric conditions.
Topics: Parvalbumins; Animals; Interneurons; Cholecystokinin; Mice; Humans; Male; Autism Spectrum Disorder; Schizophrenia; Mice, Inbred C57BL; Hippocampus; Female; Oxidative Phosphorylation; CA1 Region, Hippocampal; Macaca fascicularis
PubMed: 37443194
DOI: 10.1038/s41380-023-02153-5 -
Poultry Science Jan 2023Cholecystokinin (CCK) is widely distributed in the gastrointestinal tract and central nervous system, regulating a range of physiological functions by activating its...
Cholecystokinin (CCK) is widely distributed in the gastrointestinal tract and central nervous system, regulating a range of physiological functions by activating its receptors (CCK1R and CCK2R). Compared to those in mammals, the CCK gene and its receptors have already been cloned in various birds, such as chickens. However, knowledge regarding their functionality and tissue expression is limited. In this study, we examined the expression of CCK and its 2 receptors in chicken tissues. In addition, the functionality of the 2 receptors was investigated. Using 3 cell-based luciferase reporter systems and western blots, we demonstrated that chicken (c-) CCK1R could be potently activated by cCCK-8S but not cCCK-4, whereas cCCK2R could be activated by cCCK-8S and cCCK-4 with similar efficiency. Using RNA-sequencing, we revealed that cCCK is abundantly expressed in the testis, ileum, and several brain regions (cerebrum, midbrain, cerebellum, hindbrain, and hypothalamus). The abundant expression of CCK in the hypothalamus was further supported by immunofluorescence. In addition, cCCK1R is highly expressed in the pancreas and moderately expressed in various intestinal regions (ileum, cecum, and rectum) and the pituitary gland, whereas cCCK2R expression is primarily restricted to the brain. Our data reveal the differential specificities of CCK receptors for various CCK peptides. In combination with the differential tissue distribution of CCK and its receptors, the present study helps to understanding the physiological functions of CCK/CCKRs in birds.
Topics: Male; Animals; Cholecystokinin; Chickens; Receptors, Cholecystokinin; Intestines; Ileum; Mammals
PubMed: 36436379
DOI: 10.1016/j.psj.2022.102273