Abstract

This project examines the physiological effects and the underlying biochemical mechanisms of action of delta opioid peptides and a related protein HIT (Hibernation Induction Trigger) in tissue survival. In this fiscal year, we found that in isolated rabbit heart preparation in which hearts were subjected to 18 hrs of global ischemia, DADLE greatly enhances the functional recovery of myocardial functions. This action of DADLE is blocked by the selective delta2 opioid receptor antagonist. We also extend our finding on the tissue protective property of DADLE from the peripheral system to the central nervous system by examining if DADLE might protect against methamphetamine(METH)-induced dopaminergic (DA) neuronal damage in mouse brain. Results indicate that DADLE dose-dependently blocks the METH-induced DA damage. This action of DADLE may involves opioid receptors as opioid antagonist naltrexone partially reverses this action of DADLE. We also found that DADLE is an antioxidative agent in vitro, suggesting that part of the ation of DADLE as a protective agent against METH-induced DA neuronal damage may involve a sequestration of free radicals which are known to play a role in METH neurotoxicity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Intramural Research (Z01)
Project #
1Z01DA000263-05
Application #
6103895
Study Section
Special Emphasis Panel (CNRB)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1998
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
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
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; 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