The stimulative effects of endogenous opioids on endothelial cell proliferation, migration and angiogenesis in vitro.
The opioid peptides modulate extensive bioactivities, including pain, cardiovascular response, development and further responses. In the present study, the stimulative effects of endogenous opioid peptides on angiogenesis are evaluated in the proliferation, migration, adhesion and tube formation assays of the human umbilical vein endothelial cell (HUVEC) for the first time. Endomorphin-1, endomorphin-2 and deltorphin I at physiological concentrations could stimulate HUVECs proliferation, migration, adhesion and tube formation in a dose dependent manner; whereas, they exhibited the cytotoxic effects on HUVECs at the higher doses in these assays. Naloxone, the nonselective opioid receptor antagonist, did not influence angiogenesis when it was administrated on its own; but it could antagonize the stimulative effects of the opioid peptides on angiogenesis when it was administrated in combination with the opioid peptides. Taken altogether, the results suggested that endogenous opioid peptides (endomorphin-1 and -2 and deltorphin I) stimulated angiogenesis at the cellular level, and these effects were mediated by the opioid receptors. These data are significant for potential clinical implementation in future.
Dai
Xu
X
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, and Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou, PR China.
Song
Hong-jin
HJ
Cui
Shi-gang
SG
Wang
Ting
T
Liu
Qian
Q
Wang
Rui
R
D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000737:chemistry / Q000378:metabolism*; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D018919:Neovascularization, Physiologic; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism
D000701:Analgesics, Opioid; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu