Department of Pharmacology and Pharmacotherapy, University of Pécs, Faculty of Medicine, H-7624 Pécs, Szigeti u. 12, Hungary.
Curr Top Med Chem. 2011;11(17):2253-63. doi: 10.2174/156802611796904852.
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 counter-regulatory 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 from isolated trachea, detection of sstR4 receptors in animal and human tissue specimens, using sstR4 gene-deleted mice and investigating in detail effects of a stable peptide analogue of somatostatin (TT-232) and of 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.
通过对大鼠背根的逆行刺激，从激活的 TRPV1 表达伤害感受器释放的生长抑素被揭示出来，这为这些伤害感受器上的新型潜在药物靶点提供了证据。该综述总结了大鼠和豚鼠中新发现的生长抑素介导的、具有抗炎/镇痛作用的新型“分泌感觉”功能的功能、生化和药理学证据。为了确定负责这种功能的生长抑素受体亚型，实验集中在 sstR4 受体激动剂的作用上，因为这种亚型与 sstR1 一样，不参与内分泌调节。生长抑素和 sstR4 的参与是通过使用生长抑素抗体预处理、半胱胺耗竭生长抑素、测量血浆生长抑素样免疫反应性、从离体气管中神经释放、检测动物和人组织标本中的 sstR4 受体、使用 sstR4 基因缺失小鼠以及详细研究稳定的生长抑素类似物（TT-232）和 sstR4 受体的超高效非肽激动剂的作用来揭示的。在各种炎症和神经病理性疾病的实验模型中观察到这些 sstR4 激动剂具有有希望的镇痛、抗痛觉过敏作用，这些作用是由 TRPV1 表达的伤害感受器和参与炎症介导的非神经细胞介导的。在 sstR4 受体敲除小鼠中，观察到炎症和痛觉过敏加剧。
