The kinin system mediates hyperalgesia through the inducible bradykinin B1 receptor subtype: evidence in various experimental animal models of type 1 and type 2 diabetic neuropathy
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Bichoy H. Gabra
Abstract
Both insulin-dependent (type 1) and insulin-independent (type 2) diabetes are complex disorders characterized by symptomatic glucose intolerance due to either defective insulin secretion, insulin action or both. Unchecked hyperglycemia leads to a series of complications among which is painful diabetic neuropathy, for which the kinin system has been implicated. Here, we review and compare the profile of several experimental models of type 1 and 2 diabetes (chemically induced versus gene-prone) and the incidence of diabetic neuropathy upon aging. We discuss the efficacy of selective antagonists of the inducible bradykinin B1 receptor (BKB1-R) subtype against hyperalgesia assessed by various nociceptive tests. In either gene-prone models of type 1 and 2 diabetes, the incidence of hyperalgesia mostly precedes the development of hyperglycemia. The administration of insulin, achieving euglycemia, does not reverse hyperalgesia. Treatment with a selective BKB1-R antagonist does not affect basal nociception in most normal control rats, whereas it induces a significant time- and dose-dependent attenuation of hyperalgesia, or even restores nociceptive responses, in experimental diabetic neuropathy models. Diabetic hyperalgesia is absent in streptozotocin-induced type 1 diabetic BKB1-R knockout mice. Thus, selective antagonism of the inducible BKB1-R subtype may constitute a novel and potential therapeutic approach for the treatment of painful diabetic neuropathy.
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©2006 by Walter de Gruyter Berlin New York
Artikel in diesem Heft
- Exploring the future of local vascular and inflammatory mediators
- Genetically altered animal models in the kallikrein-kinin system
- The kinin system mediates hyperalgesia through the inducible bradykinin B1 receptor subtype: evidence in various experimental animal models of type 1 and type 2 diabetic neuropathy
- Cross-talk of the renin-angiotensin and kallikrein-kinin systems
- Which endothelium-derived factors are really important in humans?
- Kinin- and angiotensin-converting enzyme (ACE) inhibitor-mediated nitric oxide production in endothelial cells
- Anti-inflammatory effects of kinins via microglia in the central nervous system
- Platelets promote coagulation factor XII-mediated proteolytic cascade systems in plasma
- Three-dimensional structure of an AMPA receptor without associated stargazin/TARP proteins
- Dual antagonists of the bradykinin B1 and B2 receptors based on a postulated common pharmacophore from existing non-peptide antagonists
- Generation and characterization of a humanized bradykinin B1 receptor mouse
- The role of bradykinin B1 receptor on cardiac remodeling in stroke-prone spontaneously hypertensive rats (SHR-SP)
- Molecular identification and pharmacological profile of the bovine kinin B1 receptor
- Interplay of human tissue kallikrein 4 (hK4) with the plasminogen activation system: hK4 regulates the structure and functions of the urokinase-type plasminogen activator receptor (uPAR)
- Cathepsin B localizes to plasma membrane caveolae of differentiating myoblasts and is secreted in an active form at physiological pH
Artikel in diesem Heft
- Exploring the future of local vascular and inflammatory mediators
- Genetically altered animal models in the kallikrein-kinin system
- The kinin system mediates hyperalgesia through the inducible bradykinin B1 receptor subtype: evidence in various experimental animal models of type 1 and type 2 diabetic neuropathy
- Cross-talk of the renin-angiotensin and kallikrein-kinin systems
- Which endothelium-derived factors are really important in humans?
- Kinin- and angiotensin-converting enzyme (ACE) inhibitor-mediated nitric oxide production in endothelial cells
- Anti-inflammatory effects of kinins via microglia in the central nervous system
- Platelets promote coagulation factor XII-mediated proteolytic cascade systems in plasma
- Three-dimensional structure of an AMPA receptor without associated stargazin/TARP proteins
- Dual antagonists of the bradykinin B1 and B2 receptors based on a postulated common pharmacophore from existing non-peptide antagonists
- Generation and characterization of a humanized bradykinin B1 receptor mouse
- The role of bradykinin B1 receptor on cardiac remodeling in stroke-prone spontaneously hypertensive rats (SHR-SP)
- Molecular identification and pharmacological profile of the bovine kinin B1 receptor
- Interplay of human tissue kallikrein 4 (hK4) with the plasminogen activation system: hK4 regulates the structure and functions of the urokinase-type plasminogen activator receptor (uPAR)
- Cathepsin B localizes to plasma membrane caveolae of differentiating myoblasts and is secreted in an active form at physiological pH