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 organ preservation and protection. Delta opioid peptide DADLE dramatically enhanced the hypothermic preservation of isolated rat lungs. Compared to controls using Euro-Collins solution which developed pulmonary edema and hemorrhage, the DADLE-preserved lungs showed good flow, almost normal vascular resistance and good oxygenation. In isolated rabbit heart preparation in which hearts were subjected to 18 hrs of global ischemia, a 15 min preconditioning of the heart with DADLE was found to greatly enhance the functional recovery of myocardium. We are currently investigating if this action of DADLE is mediated via any specific subtype of delta opioid receptors and examining if this tissue protective property of DADLE can be seen in the central nervous system.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Intramural Research (Z01)
Project #
1Z01DA000263-04
Application #
6161719
Study Section
Special Emphasis Panel (NS)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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

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