Abstract

This project examines the physiological effects and the underlying biochemical mechanisms of the action of delta opioid peptide DADLE in cellular survival. This project will be terminated during this year in order to focus on higher priority projects. A summary of our final progress on this project is indicated as follows. The delta opioid peptide [D-Ala2,D-Leu5]enkephalin (DADLE) has been shown to be a neuroprotective agent via mechanisms that are not totally understood. We previously demonstrated that the i.p. injection of DADLE in mice causes an increase of nerve growth factor (NGF) in the brain. To further clarify the NGF-increasing action of DADLE, we examined the NGF-increasing effect of DADLE in vitro, using cultured NG-108 cells. DADLE dose-dependently increases the immunoreactive level of NGF in NG-108 cells in a bell-shape manner, with the effective DADLE concentrations in the picomolar range (0.01-100 pM). Also, DADLE at 1 pM selectively increases c-Jun and c-Fos, but not c-Rel. These results indicate that DADLE is one of the most potent agents in increasing the NGF in the biological system and that this action of DADLE involves selective increases of c-Jun and c-Fos, transcription factors that promote the NGF expression.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Intramural Research (Z01)
Project #
1Z01DA000263-12
Application #
7149286
Study Section
(CNRB)
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
2005
Total Cost
Indirect Cost

  Institution

Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Tsai, Shang-Yi; Hayashi, Teruo; Su, Tsung-Ping (2005) Picomolar concentrations of hibernation induction delta opioid peptide [D-Ala2,D-Leu5]enkephalin increase the nerve growth factor in NG-108 cells. Synapse 57:179-81
Borlongan, Cesario V; Wang, Yun; Su, Tsung-Ping (2004) Delta opioid peptide (D-Ala 2, D-Leu 5) enkephalin: linking hibernation and neuroprotection. Front Biosci 9:3392-8
Wang, Yun; Chang, Chen-Fu; Morales, Marisela et al. (2003) Diadenosine tetraphosphate protects against injuries induced by ischemia and 6-hydroxydopamine in rat brain. J Neurosci 23:7958-65
Hayashi, Teruo; Su, Tsung-Ping (2003) Chronic [D-Ala2, D-Leu5]enkephalin treatment increases the nerve growth factor in adult mouse brain. Eur J Pharmacol 464:237-9
Hayashi, Teruo; Tsao, Li-I; Su, Tsung-Ping (2002) Antiapoptotic and cytotoxic properties of delta opioid peptide [D-Ala(2),D-Leu(5)]enkephalin in PC12 cells. Synapse 43:86-94
Bolling, S F; Badhwar, V; Schwartz, C F et al. (2001) Opioids confer myocardial tolerance to ischemia: interaction of delta opioid agonists and antagonists. J Thorac Cardiovasc Surg 122:476-81
Wang, Y; Hayashi, T; Chang, C F et al. (2001) Methamphetamine potentiates ischemia/reperfusion insults after transient middle cerebral artery ligation. Stroke 32:775-82
Borlongan, C V; Zhou, F C; Hayashi, T et al. (2001) Involvement of GDNF in neuronal protection against 6-OHDA-induced parkinsonism following intracerebral transplantation of fetal kidney tissues in adult rats. Neurobiol Dis 8:636-46
Borlongan, C V; Su, T P; Wang, Y (2001) Delta opioid peptide augments functional effects and intrastriatal graft survival of rat fetal ventral mesencephalic cells. Cell Transplant 10:53-8
Hayashi, T; Hirata, H; Asanuma, M et al. (2001) Delta opioid peptide [D-Ala2, D-Leu5]enkephalin causes a near complete blockade of the neuronal damage caused by a single high dose of methamphetamine: examining the role of p53. Synapse 39:305-12

Showing the most recent 10 out of 17 publications