Abstract
Release of somatostatin into the circulation from the activated TRPV1-expressing nociceptors revealed by antidromic stimulation of dorsal roots in the rat pinpointed to a novel potential drug target on these nociceptors. The review summarizes the functional, biochemical and pharmacological evidence for a novel somatostatin-mediated counterregulatory antiinflammatory/antinociceptive “sensocrine” function in rats and guinea-pigs. To identify the somatostatin receptor subtype(s) responsible for this function, experiments were focused on actions of sstR4 receptor agonists as this subtype, similarly to sstR1, is not involved in endocrine regulation. Involvement of somatostatin and the sstR4 was revealed by using pretreatment with somatostatin antibody, depletion of somatostatin with cysteamine, measuring the plasma somatostatin-like immunoreactivity, release from nerves in vitro of the isolated trachea, detection of sstR4 receptors in animal and human tissue specimens, using sstR4 gene-deleted mice and investigating in the detail effects of a stable peptide analogue of somatostatin (TT-232) and an ultrapotent non-peptide agonist of sstR4 receptors. Promising antinociceptive, antihyperalgesic effects of these sstR4 agonists were observed in various experimental models of inflammatory and neuropathic conditions which are mediated both by TRPV1-expressing nociceptors and non-neural cells involved in mediation of inflammation. In sstR4 receptor knockout mice an aggravation of inflammation and hyperalgesia was observed.
Keywords: Capsaicin, TRPV1, TRPA1, somatostatin, antiinflammatory effect, antinociception, sensocrine effect, nociceptors, antiinflammatory/antinociceptive, sensocrine, sstR4 receptor agonists, sstR1, immunoreactivity, stable peptide analogue of somatostatin (TT-232), antihyperalgesic effects
Current Topics in Medicinal Chemistry
Title: Inhibition of the Function of TRPV1-Expressing Nociceptive Sensory Neurons by Somatostatin 4 Receptor Agonism: echanism and Therapeutical Implications
Volume: 11 Issue: 17
Author(s): Janos Szolcsanyi, Erika Pinter, Zsuzsanna Helyes and Gabor Petho
Affiliation:
Keywords: Capsaicin, TRPV1, TRPA1, somatostatin, antiinflammatory effect, antinociception, sensocrine effect, nociceptors, antiinflammatory/antinociceptive, sensocrine, sstR4 receptor agonists, sstR1, immunoreactivity, stable peptide analogue of somatostatin (TT-232), antihyperalgesic effects
Abstract: Release of somatostatin into the circulation from the activated TRPV1-expressing nociceptors revealed by antidromic stimulation of dorsal roots in the rat pinpointed to a novel potential drug target on these nociceptors. The review summarizes the functional, biochemical and pharmacological evidence for a novel somatostatin-mediated counterregulatory antiinflammatory/antinociceptive “sensocrine” function in rats and guinea-pigs. To identify the somatostatin receptor subtype(s) responsible for this function, experiments were focused on actions of sstR4 receptor agonists as this subtype, similarly to sstR1, is not involved in endocrine regulation. Involvement of somatostatin and the sstR4 was revealed by using pretreatment with somatostatin antibody, depletion of somatostatin with cysteamine, measuring the plasma somatostatin-like immunoreactivity, release from nerves in vitro of the isolated trachea, detection of sstR4 receptors in animal and human tissue specimens, using sstR4 gene-deleted mice and investigating in the detail effects of a stable peptide analogue of somatostatin (TT-232) and an ultrapotent non-peptide agonist of sstR4 receptors. Promising antinociceptive, antihyperalgesic effects of these sstR4 agonists were observed in various experimental models of inflammatory and neuropathic conditions which are mediated both by TRPV1-expressing nociceptors and non-neural cells involved in mediation of inflammation. In sstR4 receptor knockout mice an aggravation of inflammation and hyperalgesia was observed.
Export Options
About this article
Cite this article as:
Szolcsanyi Janos, Pinter Erika, Helyes Zsuzsanna and Petho Gabor, Inhibition of the Function of TRPV1-Expressing Nociceptive Sensory Neurons by Somatostatin 4 Receptor Agonism: echanism and Therapeutical Implications, Current Topics in Medicinal Chemistry 2011; 11 (17) . https://dx.doi.org/10.2174/156802611796904852
DOI https://dx.doi.org/10.2174/156802611796904852 |
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
-
Identification and Evaluation of Molecular Properties Related to Preclinical Optimization and Clinical Fate
Medicinal Chemistry Free Radicals Generated by Post-Prandial Oxidative Burst in the Early Alterations of Vascular Contractility
Clinical Immunology, Endocrine & Metabolic Drugs (Discontinued) Cancer-Specific Ligands Identified from Screening of Peptide-Display Libraries
Current Pharmaceutical Design On the Involvement of H2S in Nitroso Signaling and Other Mechanisms of H2S Action
Current Pharmaceutical Biotechnology Current Challenges and Updates on the Therapy of Fungal Infections
Current Topics in Medicinal Chemistry Membrane Ion Channels and Diabetes
Current Pharmaceutical Design Monoclonal Antibodies as Pharmacokinetic Antagonists for the Treatment of (+)-Methamphetamine Addiction
CNS & Neurological Disorders - Drug Targets Leptin-Induced Endothelial Dysfunction: A Target for Therapeutic Interventions
Current Pharmaceutical Design Transformations of Statins: Effect of Light and pH
Current Organic Chemistry Engineered Nanoparticles Against MDR in Cancer: The State of the Art and its Prospective
Current Pharmaceutical Design Active Metabolites Resulting from Decarboxylation, Reduction and Ester Hydrolysis of Parent Drugs
Current Drug Metabolism Penile Rehabilitation After Radical Prostatectomy
Current Drug Targets Modern Drug Discovery Technologies: Opportunities and Challenges in Lead Discovery
Combinatorial Chemistry & High Throughput Screening Preparation and Characterization of Diltiazem HCL Loaded Bovine Serum Albumin Nanoparticles by Desolvation Technique
Pharmaceutical Nanotechnology Quinoxalinone as a Privileged Platform in Drug Development
Mini-Reviews in Medicinal Chemistry Free Radicals in Living Systems: In Vivo Detection of Bioradicals with EPR Spectroscopy
Current Organic Chemistry A Therapeutic Connection between Dietary Phytochemicals and ATP Synthase
Current Medicinal Chemistry Estrogen and Female Lower Urinary Tract Dysfunction
Current Women`s Health Reviews Do Not Say Ever Never More: The Ins and Outs of Antiangiogenic Therapies
Current Pharmaceutical Design Mutations of mtDNA in some Vascular and Metabolic Diseases
Current Pharmaceutical Design