Abstract
Since the isolation and sequencing of cholecystokinin (CCK), considerable advances have been made in understanding the roles played by this peptide as a hormone and as a neuropeptide. CCK-1(A) and 2(B) receptor (R) cDNAs have been cloned; shortly thereafter, the naturally occurring CCK-1R gene-deficient rat (the Otsuka Long-Evans Tokushima Fatty (OLETF) rat) was discovered. This strain develops adult-onset diabetes with obesity, and has a 6847 base-pair deletion of the CCK-1R gene in which the promoter lesion and the first two exons are missing. At the same time, the genomic structures of CCK-1R in rats, mice, and humans were clarified. The CCK-1R gene consists of five exons interrupted by four introns. It has been determined that there is species- and tissue-specific CCK receptor heterogeneity of expression; in particular, there is evidence that the human pancreas does not express CCK-1R, while the pancreas in rodents primarily expresses CCK-1R. Although CCK-1R polymorphisms with amino acid changes such as 21Gly to Arg, 71 Arg to Gly, and 364 Val to Ile were discovered in subjects with obesity and diabetes mellitus, these changes occur sporadically. We identified two sequence changes, a G to T change in nucleotide – 128, and an A to G change in nucleotide – 81, in the promoter region of the CCK-1R gene. This polymorphism is considered to be a single nucleotide polymorphism (SNP) related to weight control difficulties in obese subjects as well as to psychiatric disorders. The precise molecular mechanisms of this polymorphism remain to be clarified.
Keywords: CCK-1R GENE, non-insulin-dependent diabetes mellitus, isoleucine, Obesity, alcoholics
Current Topics in Medicinal Chemistry
Title: Cholecystokinin 1(A) Receptor Polymorphisms
Volume: 7 Issue: 12
Author(s): Kyoko Miyasaka, Soichi Takiguchi and Akihiro Funakoshi
Affiliation:
Keywords: CCK-1R GENE, non-insulin-dependent diabetes mellitus, isoleucine, Obesity, alcoholics
Abstract: Since the isolation and sequencing of cholecystokinin (CCK), considerable advances have been made in understanding the roles played by this peptide as a hormone and as a neuropeptide. CCK-1(A) and 2(B) receptor (R) cDNAs have been cloned; shortly thereafter, the naturally occurring CCK-1R gene-deficient rat (the Otsuka Long-Evans Tokushima Fatty (OLETF) rat) was discovered. This strain develops adult-onset diabetes with obesity, and has a 6847 base-pair deletion of the CCK-1R gene in which the promoter lesion and the first two exons are missing. At the same time, the genomic structures of CCK-1R in rats, mice, and humans were clarified. The CCK-1R gene consists of five exons interrupted by four introns. It has been determined that there is species- and tissue-specific CCK receptor heterogeneity of expression; in particular, there is evidence that the human pancreas does not express CCK-1R, while the pancreas in rodents primarily expresses CCK-1R. Although CCK-1R polymorphisms with amino acid changes such as 21Gly to Arg, 71 Arg to Gly, and 364 Val to Ile were discovered in subjects with obesity and diabetes mellitus, these changes occur sporadically. We identified two sequence changes, a G to T change in nucleotide – 128, and an A to G change in nucleotide – 81, in the promoter region of the CCK-1R gene. This polymorphism is considered to be a single nucleotide polymorphism (SNP) related to weight control difficulties in obese subjects as well as to psychiatric disorders. The precise molecular mechanisms of this polymorphism remain to be clarified.
Export Options
About this article
Cite this article as:
Kyoko Miyasaka , Soichi Takiguchi and Akihiro Funakoshi , Cholecystokinin 1(A) Receptor Polymorphisms, Current Topics in Medicinal Chemistry 2007; 7 (12) . https://dx.doi.org/10.2174/156802607780960465
DOI https://dx.doi.org/10.2174/156802607780960465 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Anti-Inflammatory Drugs and Prediction of New Structures by Comparative Analysis
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Base Excision Repair, the Redox Environment and Therapeutic Implications
Current Molecular Pharmacology Freeze Dried Chitosan/ Poly-(Glutamic Acid) Microparticles for Intestinal Delivery of Lansoprazole
Current Drug Delivery Alternative Splicing, DNA Damage and Modulating Drugs in Radiation Therapy for Cancer
Anti-Cancer Agents in Medicinal Chemistry Recent Research Trends on Bismuth Compounds in Cancer Chemoand Radiotherapy
Current Medicinal Chemistry Evaluation of pH Triggers in situ Porous Controlled Release Micro Balloon Delivery of Amoxicillin for Eradication of Helicobacter pylori
Current Drug Delivery Strategies for Antimicrobial Drug Delivery to Biofilm
Current Pharmaceutical Design Translational Optical Imaging in Diagnosis and Treatment of Cancer
Current Pharmaceutical Biotechnology Design, Synthesis and Biological Evaluation of Palladium (II) Complexes with 1-(substituted benzyl) azetidine-3,3-dicarboxylates as Leaving Group
Medicinal Chemistry Strategies to Improve Insulin Delivery through Oral Route: A Review
Current Drug Delivery The Role of E-Cadherin Down-Regulation in Oral Cancer: CDH1 Gene Expression and Epigenetic Blockage
Current Cancer Drug Targets Ezetimibe; More Than a Low Density Lipoprotein Cholesterol Lowering Drug? An Update After 4 Years
Current Vascular Pharmacology Prodrugs for Targeted Tumor Therapies: Recent Developments in ADEPT, GDEPT and PMT
Current Pharmaceutical Design Characterization of Stem-Like Cells Directly Isolated from Freshly Resected Laryngeal Squamous Cell Carcinoma Specimens
Current Stem Cell Research & Therapy New Chalcones Containing 5-Fluorouracil Exhibiting in vitro Anti-Cancer Activity
Letters in Organic Chemistry Calix[n]arenes as Goldmines for the Development of Chemical Entities of Pharmaceutical Interest
Current Pharmaceutical Design Metabolic Features of Alcoholic Liver Disease
Reviews on Recent Clinical Trials Safety of One-week, First-line, Standard Triple Therapy for Helicobacter pylori Eradication in a Japanese Population
Current Drug Safety Peptide-Based Nanostructures for Cancer Diagnosis and Therapy
Current Medicinal Chemistry Meloxicam-loaded Phospholipid/solutol® HS15 Based Mixed Nanomicelles: Preparation, Characterization, and in vitro Antioxidant Activity
Pharmaceutical Nanotechnology