Effects of protein kinase C activator PMA on TRPV1 channels Protein kinaz C aktivatörü PMA’nın TRPV1 kanalları Üzerindeki etkileri


ÖZGÜL C.

Hacettepe University Journal of the Faculty of Pharmacy, vol.35, no.1, pp.42-73, 2015 (Scopus) identifier

  • Publication Type: Article / Article
  • Volume: 35 Issue: 1
  • Publication Date: 2015
  • Journal Name: Hacettepe University Journal of the Faculty of Pharmacy
  • Journal Indexes: Scopus
  • Page Numbers: pp.42-73
  • Keywords: Nerve cells, Oxidative stress, Protein Kinase C, Secondary messengers, TRPV1 channel agonists and antagonists
  • Istanbul Medipol University Affiliated: Yes

Abstract

TRPV1 channel, which is one of TRP super families, is a non- selective cation channel. An important part of the TRPV1 channel is located in dorsal root ganglion, vagal and trigeminal neurons. TRPV1 is activated by high temperatures, low pH and capsaicin isolated from red hot chili peppers. The activation of this channel is via temperature hence it functions in the neurons like a thermometer. Also, the chemical capsazepine is a specific blocker of TRPV1. One of the most important events for the activities in the body is primary and secondary (hormones and neurotransmitters) messenger systems. Hor mones are released by endocrine glands and they bind a specific receptor. When the hormone binds to its receptor, it leads to the release of the secondary messenger. One of the most important secondary messengers is PKC via activation of PLC. When Ca2+ ions levels are elevated in the cell, it causes the increase of the PKC levels, as well. Also, PMA agent is a phorbol ester, directly activates PKC, which in turn induces TRPV1 channels. It is well known that an increase in the amount of intracellular Ca2+ leads to an increase in oxidative stress. The activation of TRPV1 increases further the amount of intracellular Ca2+ and an increase by means of the amount of Ca2+ causes more activation of PKC. While this process continues as a positive feedback mechanism, the oxidative stress will continue to increase. If the antioxidant system is not activated or is insufficient, the cell will be directed to apoptosis. Ca2+ concentration as a result of the opening of TRPV1 via PKC activation and going beyond physiological conditions in the nerve cells can lead to a lot of diseases. In treatment of these diseases, stopping the flowing of Ca2+ via TRPV1 and activation of PKC request is self-evident. Due to the presence of a limited number of studies on this topic, investigation of the effects of antioxidant substances inhibition of TRPV1 channel activated by this mechanism will contribute to the etiology of neurological disorders’ treatment.