Abstract
Gastroduodenal HCO3 - secretion is a key process that aids in preventing acid-peptic injury. The HCO3 - secretion in rats and mice was increased in response to PGE2 as well as mucosal acidification, the latter response occurring with a concomitant enhancement of mucosal PG production. The duodenal responses to PGE2 and acid were decreased in mice lacking EP3 receptors and reduced by coadministration of an EP3 or EP4 antagonist in rats, complete inhibition being observed when the EP3 and EP4 antagonists were given together. By contrast, the gastric responses disappeared in EP1-knockout mice and were prevented by an EP1 antagonist but not other EP antagonists. Furthermore, duodenal HCO3 - secretion was stimulated by the EP3 and EP4 agonists, whereas gastric HCO3 - secretion was increased only by the EP1 agonist. In addition, the HCO3 - stimulatory effect of sulprostone (an EP1/EP3 agonist) in the duodenum was inhibited by verapamil, a Ca2+ antagonist, and enhanced by isobutyl- methylxanthine, a phosphodiesterase (PDE) inhibitor, but the response in the stomach was inhibited by verapamil and not affected by isobutylmethylxanthine. In the mouse duodenum but not stomach, the response to PGE2 was potentiated by both vinpocetine (a PDE1 inhibitor) and cilostamide (a PDE3 inhibitor). These results suggest that the HCO3 - stimulatory effect of PGE2 in the duodenum is mediated by both EP3 and EP4 receptors, being coupled intracellularly with Ca2+ and cAMP, while that in the stomach is mediated by EP1 receptors, coupled with Ca2+. In addition, both PDE1 and PDE3 are involved in the regulation of duodenal HCO3 - secretion.
Keywords: HCO3 - secretion, stomach, duodenum, prostaglandin EP receptor subtypes, mucosal protection
Current Pharmaceutical Design
Title: Prostaglandin EP Receptor Subtypes Involved in Regulating HCO3- Secretion from Gastroduodenal Mucosa
Volume: 16 Issue: 10
Author(s): Koji Takeuchi, Masafumi Koyama, Shusaku Hayashi and Eitaro Aihara
Affiliation:
Keywords: HCO3 - secretion, stomach, duodenum, prostaglandin EP receptor subtypes, mucosal protection
Abstract: Gastroduodenal HCO3 - secretion is a key process that aids in preventing acid-peptic injury. The HCO3 - secretion in rats and mice was increased in response to PGE2 as well as mucosal acidification, the latter response occurring with a concomitant enhancement of mucosal PG production. The duodenal responses to PGE2 and acid were decreased in mice lacking EP3 receptors and reduced by coadministration of an EP3 or EP4 antagonist in rats, complete inhibition being observed when the EP3 and EP4 antagonists were given together. By contrast, the gastric responses disappeared in EP1-knockout mice and were prevented by an EP1 antagonist but not other EP antagonists. Furthermore, duodenal HCO3 - secretion was stimulated by the EP3 and EP4 agonists, whereas gastric HCO3 - secretion was increased only by the EP1 agonist. In addition, the HCO3 - stimulatory effect of sulprostone (an EP1/EP3 agonist) in the duodenum was inhibited by verapamil, a Ca2+ antagonist, and enhanced by isobutyl- methylxanthine, a phosphodiesterase (PDE) inhibitor, but the response in the stomach was inhibited by verapamil and not affected by isobutylmethylxanthine. In the mouse duodenum but not stomach, the response to PGE2 was potentiated by both vinpocetine (a PDE1 inhibitor) and cilostamide (a PDE3 inhibitor). These results suggest that the HCO3 - stimulatory effect of PGE2 in the duodenum is mediated by both EP3 and EP4 receptors, being coupled intracellularly with Ca2+ and cAMP, while that in the stomach is mediated by EP1 receptors, coupled with Ca2+. In addition, both PDE1 and PDE3 are involved in the regulation of duodenal HCO3 - secretion.
Export Options
About this article
Cite this article as:
Takeuchi Koji, Koyama Masafumi, Hayashi Shusaku and Aihara Eitaro, Prostaglandin EP Receptor Subtypes Involved in Regulating HCO3- Secretion from Gastroduodenal Mucosa, Current Pharmaceutical Design 2010; 16 (10) . https://dx.doi.org/10.2174/138161210790945931
DOI https://dx.doi.org/10.2174/138161210790945931 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Blockade of Renin Angiotensin System in Heart Failure Post-Myocardial Infarction: What is the Best Therapy?
Recent Patents on Cardiovascular Drug Discovery Reperfusion Therapies in Acute Ischemic Stroke
Recent Patents on CNS Drug Discovery (Discontinued) Menopause Does Not Affect Fatty Liver Severity In Women: A Population Study in a Mediterranean Area
Endocrine, Metabolic & Immune Disorders - Drug Targets An Overview of Innovations in Analysis and Beneficial Health Effects of Wine Polyphenols
Mini-Reviews in Medicinal Chemistry Cardiovascular Disease in Systemic Lupus Erythematosus: Recent Data on Epidemiology, Risk Factors and Prevention
Current Vascular Pharmacology Vascular Dysfunction and Insulin Resistance in Aging
Current Vascular Pharmacology Monogenic Diabetes: Genetics and Relevance on Diabetes Mellitus Personalized Medicine
Current Diabetes Reviews Nutritional Approaches to Modulate Oxidative Stress in Alzheimers Disease
Current Alzheimer Research Nanocarriers Assisted siRNA Gene Therapy for the Management of Cardiovascular Disorders
Current Pharmaceutical Design Effects of Physical Exercise on Inflammatory Markers of Atherosclerosis
Current Pharmaceutical Design Recent Advances in the Synthesis of Biologically Active Cinnoline, Phthalazine and Quinoxaline Derivatives
Current Organic Chemistry Periodontitis, Endothelial Dysfunction and Atherosclerosis
Vascular Disease Prevention (Discontinued) Cardiovascular Proteomics
Current Proteomics Role of the Renin-Angiotensin-Aldosterone System in the Pathogenesis of Atherosclerosis
Current Pharmaceutical Design Editorial: Effective Bio-EconomicApproaches for StemCell Therapy and Regenerative Medicine
Current Stem Cell Research & Therapy Non-Vitamin K Oral Anticoagulant Drugs for Stroke Prevention in Patients with Atrial Fibrillation and Chronic Kidney Disease
Current Medicinal Chemistry Dietary Fat and Hypertension: A Novel Approach Through the Proteolytic Regulatory Enzymes of the Renin-Angiotensin-System
Cardiovascular & Hematological Agents in Medicinal Chemistry Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) and LDL Lowering in the Contemporary Management of Dyslipidemia
Cardiovascular & Hematological Agents in Medicinal Chemistry Editorial (Thematic Issue: Modifying Cardiovascular Risk Factors: Newer Advances in Cardiovascular Metabolism and Diagnostic Technologies)
Current Pharmaceutical Design <i>Thespesia populnea</i>: An Ethnomedicinal, Phytochemical and Pharmacological Review
The Natural Products Journal