TY - JOUR
T1 - Differential neurotoxicity of etorphine-like opiates
T2 - Lack of correlation with their ability to activate opiate receptors
AU - Ren, Xiu Hai
AU - Zhao, Jian
AU - Pu, Lu
AU - Ling, Kun
AU - Yin, De Ling
AU - Pei, Gang
N1 - Funding Information:
This study was supported by research grants from Natural Science Foundation of China (39630130 and 39625015), Chinese Academy of Sciences (KY951-A1-301-01-05), and German Max-Planck Society. The authors thank Li-Zhen Jiang, Ya-Lan Wu, Guo-Bin Bao, Yong-Qin Wu, Wei Hu and Yan-Ping Wang for technical assistance.
PY - 1998/5/15
Y1 - 1998/5/15
N2 - The present study was undertaken to compare the neurotoxic effects of three etorphine-like opiates (etorphine, dihydroetorphine, and another derivative of oripavine) and heroin with their ability to activate opiate receptors in human neuroblastoma cell line SK-N-SH as well as in two other neuronal cell lines. Neurotoxicity was measured by using [3H]-thymidine incorporation analysis, cell viability measurement and Cytosensor microphysiometry. It was found that, in spite of the very similar molecular structures of these opiates, they displayed significant differences in cytotoxicity, with etorphine and another derivative of oripavine possessing high potency but dihydroetorphine and heroin little effect. However, neurotoxic potency of the opiates was not directly correlated to their ability to activate opioid receptors, as determined by [35S]-guanylyl-5'- O-(γ-tho)-triphosphate binding assay. These findings provide clear evidence of differential neurotoxicity of etorphine-like opiates, and suggest that the neurotoxicity is not closely related to the molecular configuration required as opioid receptor agonist but is probably associated with the present of a double bond in the structure.
AB - The present study was undertaken to compare the neurotoxic effects of three etorphine-like opiates (etorphine, dihydroetorphine, and another derivative of oripavine) and heroin with their ability to activate opiate receptors in human neuroblastoma cell line SK-N-SH as well as in two other neuronal cell lines. Neurotoxicity was measured by using [3H]-thymidine incorporation analysis, cell viability measurement and Cytosensor microphysiometry. It was found that, in spite of the very similar molecular structures of these opiates, they displayed significant differences in cytotoxicity, with etorphine and another derivative of oripavine possessing high potency but dihydroetorphine and heroin little effect. However, neurotoxic potency of the opiates was not directly correlated to their ability to activate opioid receptors, as determined by [35S]-guanylyl-5'- O-(γ-tho)-triphosphate binding assay. These findings provide clear evidence of differential neurotoxicity of etorphine-like opiates, and suggest that the neurotoxicity is not closely related to the molecular configuration required as opioid receptor agonist but is probably associated with the present of a double bond in the structure.
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U2 - 10.1016/S0041-0101(97)00109-8
DO - 10.1016/S0041-0101(97)00109-8
M3 - Article
C2 - 9655634
AN - SCOPUS:0031843048
SN - 0041-0101
VL - 36
SP - 735
EP - 743
JO - Toxicon
JF - Toxicon
IS - 5
ER -