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
-
Medicinal Chemistry Approaches of Controlling Gastrointestinal Side Effects of Non-Steroidal Anti-Inflammatory Drugs. Endogenous Protective Mechanisms and Drug Design
Medicinal Chemistry Combined Anticancer Therapies: An Overview of the Latest Applications
Anti-Cancer Agents in Medicinal Chemistry PPARs as Drug Targets to Modulate Inflammatory Responses?
Current Drug Targets - Inflammation & Allergy MicroRNA-183 Functions As an Oncogene by Regulating PDCD4 in Gastric Cancer
Anti-Cancer Agents in Medicinal Chemistry Polynuclear Ruthenium, Osmium and Gold Complexes. The Quest for Innovative Anticancer Chemotherapeutics
Current Topics in Medicinal Chemistry Free Radicals in Diseases and Potential Role of Phytoconstituents-A Cause with Emerging Importance
Current Chemical Biology Synthesis and Anti-Cancer Activities of Aryl Benzyl Ethers with Fluoro Substituents
Letters in Drug Design & Discovery Cholinergic Targets in Lung Cancer
Current Pharmaceutical Design Protective Effect of Annurca Apple Extract Against Oxidative Damage in Human Erythrocytes
Current Nutrition & Food Science Histone and Non-Histone Targets of Dietary Deacetylase Inhibitors
Current Topics in Medicinal Chemistry Recent Advances in Epitope Design for Immunotherapy of Cancer
Recent Patents on Anti-Cancer Drug Discovery CD24, A Review of its Role in Tumor Diagnosis, Progression and Therapy
Current Gene Therapy Marine Bromopyrrole Alkaloids: Synthesis and Diverse Medicinal Applications
Current Topics in Medicinal Chemistry Emerging Therapeutic Potential of Whey Proteins and Peptides
Current Pharmaceutical Design Upregulation of Cytoskeleton Protein and Extracellular Matrix Protein Induced by Stromal-Derived Nitric Oxide Promotes Lung Cancer Invasion and Metastasis
Current Molecular Medicine Low-Cost Anti-HIV Compounds: Potential Application for AIDS Therapy in Developing Countries
Current Pharmaceutical Design Efficacy and Safety of Mesenchymal Stromal Cells Therapy for COVID-19 Infection: A Systematic Review and Meta-analysis
Current Stem Cell Research & Therapy Pharmacogenetic Applications of the Post Genomic Era
Current Pharmaceutical Biotechnology Are Catechins, Polyphenols in Tea, Good for Your Health?
Current Nutrition & Food Science Voltage-Dependent Potassium Channels Kv1.3 and Kv1.5 in Human Cancer
Current Cancer Drug Targets