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.
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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 |
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