Journal of Veterinary Science

The Korean Society of Veterinary Science (대한수의학회)
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Inhibition of angiotensin converting enzyme increases PKCβI isoform expression via activation of substance P and bradykinin receptors in cultured astrocytes of mice

  • Jae-Gyun Choi (Department of Physiology and Medical Science, College of Medicine and Brain Research Institute, Chungnam National University) ;
  • Sheu-Ran Choi (Department of Pharmacology, Catholic Kwandong University College of Medicine) ;
  • Dong-Wook Kang (Department of Physiology and Medical Science, College of Medicine and Brain Research Institute, Chungnam National University) ;
  • Hyun Jin Shin (Department of Physiology and Medical Science, College of Medicine and Brain Research Institute, Chungnam National University) ;
  • Miae Lee (Department of Physiology and Medical Science, College of Medicine and Brain Research Institute, Chungnam National University) ;
  • Jungmo Hwang (Department of Orthopaedic Surgery, College of Medicine, Chungnam National University) ;
  • Hyun-Woo Kim (Department of Physiology and Medical Science, College of Medicine and Brain Research Institute, Chungnam National University)
  • Received : 2022.11.24
  • Accepted : 2023.02.14
  • Published : 2023.03.31
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Abstract

Background: Angiotensin-converting enzyme inhibitor (ACEi) inhibits the catalysis of angiotensin I to angiotensin II and the degradation of substance P (SP) and bradykinin (BK). While the possible relationship between ACEi and SP in nociceptive mice was recently suggested, the effect of ACEi on signal transduction in astrocytes remains unclear. Objectives: This study examined whether ACE inhibition with captopril or enalapril modulates the levels of SP and BK in primary cultured astrocytes and whether this change modulates PKC isoforms (PKCα, PKCβI, and PKCε) expression in cultured astrocytes. Methods: Immunocytochemistry and Western blot analysis were performed to examine the changes in the levels of SP and BK and the expression of the PKC isoforms in primary cultured astrocytes, respectively. Results: The treatment of captopril or enalapril increased the immunoreactivity of SP and BK significantly in glial fibrillary acidic protein-positive cultured astrocytes. These increases were suppressed by a pretreatment with an angiotensin-converting enzyme. In addition, treatment with captopril increased the expression of the PKCβI isoform in cultured astrocytes, while there were no changes in the expression of the PKCα and PKCε isoforms after the captopril treatment. The captopril-induced increased expression of the PKCβI isoform was inhibited by a pretreatment with the neurokinin-1 receptor antagonist, L-733,060, the BK B1 receptor antagonist, R 715, or the BK B2 receptor antagonist, HOE 140. Conclusions: These results suggest that ACE inhibition with captopril or enalapril increases the levels of SP and BK in cultured astrocytes and that the activation of SP and BK receptors mediates the captopril-induced increase in the expression of the PKCβI isoform.

Keywords

Acknowledgement

This research was supported by Chungnam National University, Chungnam National University Hospital Research Fund (2021) and the National Research Foundation of Korea grant funded by the Korea government (NRF-2021R1F1A1062509).

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