scholarly journals Cholecystokinin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Margery Beinfeld ◽  
Quan Chen ◽  
Fan Gao ◽  
Roger A. Liddle ◽  
Laurence J. Miller ◽  
...  
Keyword(s):  
Receptor Subtypes ◽  
Peripheral Tissues ◽  
Cck Receptors ◽  
Endogenous Peptides ◽  
Cck1 Receptor ◽  
Cholecystokinin Receptors ◽  
Alternatively Spliced ◽  
The Central Nervous System ◽  
Carboxyl Terminal ◽  
Cck2 Receptor

Cholecystokinin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on CCK receptors [89]) are activated by the endogenous peptides cholecystokinin-8 (CCK-8), CCK-33, CCK-58 and gastrin (gastrin-17). There are only two distinct subtypes of CCK receptors, CCK1 and CCK2 receptors [63, 123], with some alternatively spliced forms most often identified in neoplastic cells. The CCK receptor subtypes are distinguished by their peptide selectivity, with the CCK1 receptor requiring the carboxyl-terminal heptapeptide-amide that includes a sulfated tyrosine for high affinity and potency, while the CCK2 receptor requires only the carboxyl-terminal tetrapeptide shared by each CCK and gastrin peptides. These receptors have characteristic and distinct distributions, with both present in both the central nervous system and peripheral tissues.

Cholecystokinin and gastrin peptides stimulate ODC activity in a rat pancreatic cell line

1989 ◽  
Vol 256 (5) ◽  
pp. G846-G850 ◽  
Author(s):  
J. L. Scemama ◽  
L. De Vries ◽  
L. Pradayrol ◽  
C. Seva ◽  
H. Tronchere ◽  
...  
Keyword(s):  
Cell Line ◽  
Ornithine Decarboxylase ◽  
Radioligand Binding ◽  
Pancreatic Acinar Cell ◽  
Trophic Factors ◽  
Decarboxylase Activity ◽  
Pancreatic Cell ◽  
Peripheral Tissues ◽  
Cck Receptors ◽  
The Central Nervous System

Recent studies have demonstrated that cholecystokinin (CCK) receptors are heterologous in peripheral tissues and in the central nervous system and that CCK-gastrin (CCK-G) peptides are potent trophic factors for the gastrointestinal tract. In the present study we used 125I-labeled gastrin and 125I-labeled CCK to demonstrate the heterogeneity of CCK receptors on a rat pancreatic acinar cell line (AR4-2J) and analyze the role of these receptors in increasing the activity of ornithine decarboxylase. Pharmacological analysis of radioligand binding fit well with the presence of two different receptors: 1) a CCK-selective receptor having the characteristics of the CCK receptor present on normal pancreatic cells and 2) a high-affinity, low-selectivity CCK-G binding site that interacts with all CCK-G peptides sulfated and nonsulfated. CCK-G peptides stimulate ornithine decarboxylase activity with the following order of potencies (EC50): G-(2-17)-ds (0.1 nM) greater than or equal to CCK-9 (0.25 nM) greater than or equal to pentagastrin (0.4 nM) greater than CCK-4 (6 nM). This stimulation was not inhibited by CCK antagonist (asperlicin) at a concentration range that blocks the CCK receptor but does not compete with 125I-labeled gastrin binding to the CCK-G receptor. These results, obtained with CCK-G agonists and antagonists, demonstrate that ornithine decarboxylase stimulation in these cells is mediated via the CCK-G receptor.

scholarly journals Characterisation, localisation and expression of porcine TACR1, TACR2 and TACR3 genes

2017 ◽  
Vol 62 (No. 8) ◽  
pp. 443-455 ◽  
Author(s):  
A. Jakimiuk ◽  
P. Podlasz ◽  
M. Chmielewska-Krzesinska ◽  
K. Wasowicz
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
In Silico Analysis ◽  
Amino Acid Sequences ◽  
Chromosome 8 ◽  
Receptor Subtypes ◽  
Peripheral Tissues ◽  
Neurokinin Receptors ◽  
Tachykinin Receptor ◽  
The Central Nervous System

Substance P is involved in many physiological and pathophysiological processes. This functional diversity is mediated by three neurokinin receptor subtypes (NK1R, NK2R and NK3R) encoded by the TACR1, TACR2 and TACR3 genes, respectively. Despite the increasing interest in using pigs (Sus scrofa) to study human disease mechanisms, the sequences of these receptors are still unconfirmed or in the case of the NK1 receptor, not yet even unpredicted. We employed in silico analysis to define the localisation of the porcine tachykinin receptor genes, and to predict the structures and amino acid sequences of the respective proteins. A reverse transcription polymerase chain reaction (RT-PCR) assay was performed to analyse the expression of tachykinin receptor genes in different porcine tissues. The data show that the TACR1 gene is located on chromosome 3, TACR2 on chromosome 14 and TACR3 on chromosome 8. All three genes encode proteins with structures that incorporate features of G-protein-coupled receptors with sizes of 407, 381 and 464 amino acids, respectively. The receptors display a high degree of similarity to other mammalian neurokinin receptors. The NK1R subtype is expressed in both the central nervous system and peripheral tissues, while NK2R expression seems to be localised mostly to peripheral tissues. The expression of NK3R is found mainly in the central nervous system. This report provides for the first time the results of a comprehensive analysis of the structure and distribution of porcine NK1R, as well as other porcine neurokinin receptors and their genes. We hope that our data may offer an invaluable foundation for the future studies on the function of diverse tachykinin peptides in the central nervous system and peripheral tissues.

Cholecystokinin receptors

1995 ◽  
Vol 269 (5) ◽  
pp. G628-G646 ◽  
Author(s):  
S. A. Wank
Keyword(s):  
Function Analysis ◽  
Receptor Gene ◽  
Wide Distribution ◽  
Receptor Expression ◽  
Receptor Subtypes ◽  
Cck Receptors ◽  
High Affinity ◽  
Recombinant Receptor ◽  
Receptor Pharmacology ◽  
Specific Variation

The cholecystokinin (CCK) and gastrin families of peptides act as hormones and neuropeptides on central and peripheral CCK receptors to mediate secretion and motility in the gastrointestinal (GI) tract in the physiological response to a normal meal. CCK and its receptors are also widely distributed in the central nervous system (CNS) and contribute to the regulation of satiety, anxiety, analgesia, and dopamine-mediated behavior. Although the wide distribution, myriad number of functions, and reported pharmacological heterogeneity of CCK receptors would suggest a large number of receptor subtypes, the application of modern molecular biological techniques has identified two CCK receptors, CCK-A receptor (CCK-AR) and CCK-B receptor (CCK-BR), that mediate the actions of CCK and gastrin; gastrin receptors have been found to be identical to CCK-BR. CCK-AR, found predominantly in the GI system and select areas of the CNS, have high affinity for CCK and the nonpeptide antagonist L-364,718, whereas CCK-BR, found predominantly in the CNS and select areas of the GI system, have high affinity for CCK and gastrin and the nonpeptide antagonist L-365,260. Both CCK-AR and CCK-BR are highly conserved between species, although there is some tissue-specific variation in expression. Recombinant receptor expression faithfully reproduces the native receptor pharmacology and signal transduction pathways, allowing direct comparisons of receptor function between species as well as serving as a convenient source of receptor. Our present knowledge of the chromosomal localization, receptor gene structure, and primary sequence will allow further studies in disease association, receptor regulation, and structure-function analysis.

Isolated premature menarche in two siblings with Neurofibromatosis type 1

2020 ◽  
Vol 33 (6) ◽  
pp. 813-816
Author(s):  
James Blackburn ◽  
Mohammed Didi ◽  
Shivaram Avula ◽  
Senthil Senniappan
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Pubertal Timing ◽  
Genetic Disorder ◽  
Pubertal Development ◽  
Neurofibromatosis Type ◽  
Malignant Tumours ◽  
Peripheral Tissues ◽  
Paediatric Endocrinology ◽  
The Central Nervous System

AbstractObjectivesNeurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder, caused by mutation in NF1. The condition is typified by the development of benign and malignant tumours in both the central nervous system and peripheral tissues. Isolated menarche is a sub-classification of incomplete isosexual precocious puberty typified by menarche in girls with no other features of pubertal development. The effects of NF1 on pubertal timing are poorly understood, we report two siblings with NF1 and apparent abnormal pubertal development.Case PresentationTwo siblings were referred to the tertiary paediatric endocrinology clinic at 6 and 7 years of age with recurrent, cyclical vaginal bleeding. There was a strong family history of NF1, the mother of the siblings and two brothers were also diagnosed at a young age. On examination both patients were prepubertal at presentation. Both siblings underwent a gonadotrophin releasing hormone test, which revealed a follicle-stimulating hormone dominant (prepubertal) response. The features were suggestive of isolated premature menarche as no other cause was identified. The elder sibling established menarche and developed signs of consonant pubertal development at 12 years of age. The younger sibling remains under regular follow-up.ConclusionsNF1 has previously been associated with alterations in pubertal timing. We report, for the first time, two siblings with NF1 who presented with isolated menarche.

scholarly journals Novel Facet of an Old Dietary Molecule? Direct Influence of Caffeine on Glucose and Biogenic Amine Handling by Human Adipocytes

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3831
Author(s):  
Wiem Haj Ahmed ◽  
Nathalie Boulet ◽  
Anaïs Briot ◽  
Barry J. Ryan ◽  
Gemma K. Kinsella ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Amine Oxidase ◽  
Human Adipose Tissue ◽  
Lipid Solubility ◽  
Human Adipocytes ◽  
Peripheral Tissues ◽  
Amine Oxidation ◽  
High Lipid ◽  
The Central Nervous System ◽  
High Lipid Solubility

Caffeine is a plant alkaloid present in food and beverages consumed worldwide. It has high lipid solubility with recognized actions in the central nervous system and in peripheral tissues, notably the adipose depots. However, the literature is scant regarding caffeine’s influence on adipocyte functions other than lipolysis, such as glucose incorporation into lipids (lipogenesis) and amine oxidation. The objective of this study was to explore the direct effects of caffeine and of isobutylmethylxanthine (IBMX) on these adipocyte functions. Glucose transport into fat cells freshly isolated from mice, rats, or humans was monitored by determining [3H]-2-deoxyglucose (2-DG) uptake, while the incorporation of radiolabeled glucose into cell lipids was used as an index of lipogenic activity. Oxidation of benzylamine by primary amine oxidase (PrAO) was inhibited by increasing doses of caffeine in human adipose tissue preparations with an inhibition constant (Ki) in the millimolar range. Caffeine inhibited basal and insulin-stimulated glucose transport as well as lipogenesis in rodent adipose cells. The antilipogenic action of caffeine was also observed in adipocytes from mice genetically invalidated for PrAO activity, indicating that PrAO activity was not required for lipogenesis inhibition. These caffeine inhibitory properties were extended to human adipocytes: relative to basal 2-DG uptake, set at 1.0 ± 0.2 for 6 individuals, 0.1 mM caffeine tended to reduce uptake to 0.83 ± 0.08. Insulin increased uptake by 3.86 ± 1.11 fold when tested alone at 100 nM, and by 3.21 ± 0.80 when combined with caffeine. Our results reinforce the recommendation of caffeine’s potential in the treatment or prevention of obesity complications.

scholarly journals Adiponectin Controls Nutrient Availability in Hypothalamic Astrocytes

2021 ◽  
Vol 22 (4) ◽  
pp. 1587
Author(s):  
Nuri Song ◽  
Da Yeon Jeong ◽  
Thai Hien Tu ◽  
Byong Seo Park ◽  
Hye Rim Yang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adipose Tissue ◽  
Nutrient Availability ◽  
Acid Oxidation ◽  
Cell Type ◽  
Metabolic Processes ◽  
Nutrient Metabolism ◽  
Peripheral Tissues ◽  
The Central Nervous System

Adiponectin, an adipose tissue-derived hormone, plays integral roles in lipid and glucose metabolism in peripheral tissues, such as the skeletal muscle, adipose tissue, and liver. Moreover, it has also been shown to have an impact on metabolic processes in the central nervous system. Astrocytes comprise the most abundant cell type in the central nervous system and actively participate in metabolic processes between blood vessels and neurons. However, the ability of adiponectin to control nutrient metabolism in astrocytes has not yet been fully elucidated. In this study, we investigated the effects of adiponectin on multiple metabolic processes in hypothalamic astrocytes. Adiponectin enhanced glucose uptake, glycolytic processes and fatty acid oxidation in cultured primary hypothalamic astrocytes. In line with these findings, we also found that adiponectin treatment effectively enhanced synthesis and release of monocarboxylates. Overall, these data suggested that adiponectin triggers catabolic processes in astrocytes, thereby enhancing nutrient availability in the hypothalamus.

Cholecystokinin octapeptide analogues suppress food intake via central CCK-A receptors in mice

1993 ◽  
Vol 265 (3) ◽  
pp. R481-R486 ◽  
Author(s):  
Y. Hirosue ◽  
A. Inui ◽  
A. Teranishi ◽  
M. Miura ◽  
M. Nakajima ◽  
...  
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Rank Order ◽  
Peripheral Circulation ◽  
Inhibitory Effect ◽  
Peripheral Tissues ◽  
Cholecystokinin Octapeptide ◽  
The Central Nervous System ◽  
The Difference ◽  
The Brain

To examine the mechanism of the satiety-producing effect of cholecystokinin (CCK) in the central nervous system, we compared the potency of intraperitoneally (ip) or intracerebroventricularly (icv) administered CCK-8 and its analogues on food intake in fasted mice. The icv administration of a small dose of CCK-8 (0.03 nmol/brain) or of Suc-(Thr28, Leu29, MePhe33)-CCK-7 (0.001 nmol/brain) suppressed food intake for 20 min, whereas CCK-8 (1 nmol/kg, which is equivalent to 0.03 nmol/brain) or Suc-(Thr28, Leu29, MePhe33)-CCK-7 (1 nmol/kg) had satiety effect after ip administration. Dose-response studies indicated the following rank order of potency: Suc-CCK-7 > or = Suc-(Thr28, Leu29, MePhe33)-CCK-7 > or = CCK-8 > or = (Nle28,31)-CCK-8 >> desulfated CCK-8 = CCK-4 = 0 in the case of ip administration and Suc-(Thr28, Leu29, MePhe33)-CCK-7 >> Suc-CCK-7 > or = CCK-8 > or = (Nle28,31)-CCK-8 >> desulfated CCK-8 = CCK-4 = 0 in the case of icv administration. The selective CCK-A receptor antagonist MK-329 reversed the inhibitory effect of the centrally as well as peripherally administered CCK-8, or of Suc-(Thr28, Leu29, MePhe33)-CCK-7, whereas the selective CCK-B receptor antagonist L-365260 did not. The icv administered CCK-8 did not appear in the peripheral circulation. These findings suggest the participation of CCK-A receptors in the brain in mediating the satiety effect of CCK and the difference in CCK-A receptors in the brain and peripheral tissues.

Satiety induced by endogenous and exogenous cholecystokinin is mediated by CCK-A receptors in mice

1992 ◽  
Vol 262 (4) ◽  
pp. R574-R578 ◽  
Author(s):  
S. C. Weatherford ◽  
F. Y. Chiruzzo ◽  
W. B. Laughton
Keyword(s):  
Intraperitoneal Injection ◽  
Sucrose Solution ◽  
Intraperitoneal Administration ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Sucrose Intake ◽  
Sucrose Consumption ◽  
Minimal Effective Dose ◽  
Cck Receptors ◽  
Related Increase

To investigate the relative participation of peripheral (CCK-A) and central (CCK-B) cholecystokinin (CCK) receptors in satiety induced by endogenous CCK, we examined the effect of the CCK-A antagonist MK-329 (10-315 micrograms/kg) and the CCK-B antagonist L 365260 (0.1-315 micrograms/kg) on intake of a 20% sucrose solution in mildly food-deprived mice. Intraperitoneal injection of MK-329 elicited a dose-related increase in sucrose consumption with a minimal effective dose of 31.5 micrograms/kg. This dose increased sucrose intake 23% and the highest dose tested, 315 micrograms/kg, increased sucrose intake 63% above baseline. In contrast to MK-329, intraperitoneal administration of L 365260 had no effect on sucrose intake at doses up to 315 micrograms/kg. To examine the contribution of these two CCK receptor subtypes in satiety induced by exogenous CCK, CCK-8 (8 micrograms/kg) was administered alone and in combination with MK-329 and L 365260. MK-329 (10 micrograms/kg) significantly attenuated the satiety effect of CCK-8, and L 365260 (100 micrograms/kg) was without effect. These results suggest that the peripheral CCK receptor subtype mediates satiety induced by endogenous and exogenous CCK in the mouse.

scholarly journals Importance and prospects for design of selective muscarinic agonists

2008 ◽  
pp. S39-S47
Author(s):  
J Jakubík ◽  
P Michal ◽  
E Machová ◽  
V Doležal
Keyword(s):  
Binding Sites ◽  
Natural Aging ◽  
Receptor Activation ◽  
Receptor Subtypes ◽  
Muscarinic Agonists ◽  
Amyloidogenic Processing ◽  
M1 Receptor ◽  
The Central Nervous System ◽  
M1 Agonist ◽  
Stimulation Of

There are five subtypes of muscarinic receptors that serve various important physiological functions in the central nervous system and the periphery. Mental functions like attention, learning, and memory are attributed to the muscarinic M1 subtype. These functions decline during natural aging and an early deficit is typical for Alzheimer s disease. In addition, stimulation of the M1 receptor increases non-amyloidogenic processing of the amyloid precursor protein and thus prevents accumulation of noxious beta-amyloid fragments. The selectivity of classical muscarinic agonists among receptor subtypes is very low due to the highly conserved nature of the orthosteric binding site among receptor subtypes. Herein we summarize some recent studies with the functionally-selective M1 agonist xanomeline that indicate complex pharmacological profile of this drug that includes interactions with and activation of receptor from both orthosteric and ectopic binding sites, and the time-dependent changes of ligand binding and receptor activation. These findings point to potential profitability of exploitation of ectopic ligands in the search for truly selective muscarinic receptor agonists.

scholarly journals Social Isolation: How Can the Effects on the Cholinergic System Be Isolated?

2021 ◽  
Vol 12 ◽  
Author(s):  
Jaromir Myslivecek
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Social Isolation ◽  
Cholinergic System ◽  
System Response ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Cholinergic Signaling ◽  
The Central Nervous System

Social species form organizations that support individuals because the consequent social behaviors help these organisms survive. The isolation of these individuals may be a stressor. We reviewed the potential mechanisms of the effects of social isolation on cholinergic signaling and vice versa how changes in cholinergic signaling affect changes due to social isolation.There are two important problems regarding this topic. First, isolation schemes differ in their duration (1–165 days) and initiation (immediately after birth to adulthood). Second, there is an important problem that is generally not considered when studying the role of the cholinergic system in neurobehavioral correlates: muscarinic and nicotinic receptor subtypes do not differ sufficiently in their affinity for orthosteric site agonists and antagonists. Some potential cholinesterase inhibitors also affect other targets, such as receptors or other neurotransmitter systems. Therefore, the role of the cholinergic system in social isolation should be carefully considered, and multiple receptor systems may be involved in the central nervous system response, although some subtypes are involved in specific functions. To determine the role of a specific receptor subtype, the presence of a specific subtype in the central nervous system should be determined using search in knockout studies with the careful application of specific agonists/antagonists.

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