The 5-HT1A receptor agonist Bay X 3702 inhibits apoptosis induced by serum deprivation in cultured neurons

被引:40
作者
Ahlemeyer, B [1 ]
Glaser, A [1 ]
Schaper, C [1 ]
Semkova, I [1 ]
Krieglstein, J [1 ]
机构
[1] Univ Marburg, Inst Pharmakol & Toxikol, Fachbereich Pharm, D-35032 Marburg, Germany
关键词
apoptosis; chick neuron; NGF (nerve growth factor); neuroprotection; serum deprivation; 5-HT1A receptor agonist;
D O I
10.1016/S0014-2999(99)00136-3
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We examined whether the highly selective 5-HT1A receptor agonist (-)-(R)-2-[4-[[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl] amino]butyl]-11,2-benz-isothiazol-3(2H)-one I,l-dioxide monohydrochloride (Bay x 3702) could inhibit neuronal apoptosis induced by serum deprivation. In primary cultures of chick embryonic neurons and in mixed neuronal/glial cultures from neonatal rat hippocampus, Bay x 3702 (1 mu M) rescued serum-deprived neurons from apoptosis. The antiapoptotic effect of Bay x 3702 (1 mu M) was blocked in chick neurons by the selective 5-MT1A receptor antagonists 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazin]ethyl]-N-2-pylidinyl-benzamide hydrochloride (p-MPPI, 10 mu M) and 4-[3-benzotriazol-1-propyl]-1-(2-methoxyphenyl)-piperazine (BPMP, 10 mu M) as well as by anti-nerve growth factor (anti-NGF) antibodies and in rat neurons by N-[2-[4-(9-methoxy)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexane-carboxamide trihydrochloride (WAY 100635, 10 mu M). We found only under control conditions (medium with serum), but not in serum-deprived cultures, that NGF secretion was 6-fold increased by Bay x 3702 (1 mu M) compared to untreated cultures. Additionally, Bay x 3702 (4 mu g/kg i.v.), infused within a period of 4 h, significantly increased the NGF content of the rat hippocampus, but not of the striatum. In summary, our data suggest that Bay x 3702 inhibited growth factor withdrawal-induced apoptosis by the stimulation of 5-HT1A receptors and that the NGF signalling pathway is involved in the mechanism of action. (C) 1999 Elsevier Science B.V. All rights reserved.
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页码:211 / 216
页数:6
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