Effect of Peptidase Inhibitors on Dynorphin A (1-17) or (1-13)-Induced Antinociception and Toxicity at Spinal Level
| Autor: | Mariko Watanabe, Takugi Kan, Kenji Ito, Mitsumasa Matsuda, Toshiyasu Suzuki, Shigeru Takahashi, Junko Ajimi, M Miura, Masanobu Yoshikawa, Hiroyuki Kobayashi |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty Dynorphin Pharmacology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Amastatin Internal medicine medicine Phosphoramidon Dynorphin A respiratory system 030104 developmental biology Allodynia Endocrinology Nociception chemistry Opioid embryonic structures Toxicity medicine.symptom 030217 neurology & neurosurgery circulatory and respiratory physiology medicine.drug |
| Zdroj: | Pharmacology & Pharmacy. :33-51 |
| ISSN: | 2157-9431 2157-9423 |
| DOI: | 10.4236/pp.2017.82003 |
| Popis: | Our group has earlier demonstrated that three enzymes sensitive to peptidase inhibitors (PIs), amastatin (A)-, captopril (C)-, and phosphoramidon (P), played an important role in inactivation of enkephalins at the spinal level. Dynorphin-converting enzyme (DCE) hydrolyzes dynorphin (Dyn) A (1-17) or Dyn A (1-13) mainly at the Arg6-Arg7 bond. Dynorphin A and its derived peptides interact with opioid and glutamate receptors at their N- and C-terminals, respectively. The purpose of the present study was to evaluate the antinociceptive potency and toxicity of intrathecal administered Dyn A (1-17), Dyn A (1-13), or Dyn A (1-6) under pretreatment with ACP and/or the DCE inhibitor p-hydroxymercuribenzoate (PHMB). The effect of these PIs on Dyn A (1-17)-induced inhibition of electrically-evoked contractions in mouse vas deferens was also investigated. The inhibitory potency of Dyn A (1-17) on electrically-evoked contractions in mouse vas deferens under pretreatment with ACP was higher than that with AC, AP, or CP. Pretreatment with ACP augmented Dyn A (1-17) or (1-13)-induced antinociception by approximately 50- or 30-fold with no sign of allodynia when administered intrathecally at low doses. Pretreatment with ACP and PHMB induced neuropathy. These findings showed that intrathecal administration of low-dose Dyn A (1-17) or DynA (1-13) increased antinociception under pretreatment with ACP, but without signs of allodynia in rat. |
| Databáze: | OpenAIRE |
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