SNV, a lipophilic superactive VIP analog, acts through cGMP to promote neuronal survival

被引:22
作者
Ashur-Fabian, O
Perl, O
Lilling, G
Fridkin, M
Gozes, I [1 ]
机构
[1] Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel
[2] Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel
关键词
vasoactive intestinal peptide (VIP); Stearyl-Nle(17)-VIP (SNV); cyclic guanosine monophosphate (cGMP); immunocytochemistry; radioimmunoassays (RIA); enzymeimmunoassays (EIA); neuronal survival;
D O I
10.1016/S0196-9781(99)00017-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The current study explored whether the neuroprotective effects of vasoactive intestinal peptide (VIP) and its analog Stearyl-Nle(17)-VIP (SNV) were mediated through cGMP. SNV, was previously found to be 100-fold more potent than VIP in providing neuroprotection. Neuronal survival was assessed in rat cerebral critical cultures. A cGMP antagonist (RP-8-pCPT-cGMPS, 10(-12)-10(-9) M) reduced the number of surviving neurons (40-60%), this decline was spared in the presence of SNV (10(-13) M). A cGMP agonist (Sp-8-pCPT-cGMPS, 10(-14)-10(-8) M) and SNV (10(-16)-10(-8) M) both provided significant neuroprotection against 10(-12) M of the cGMP antagonist. Immunoassays indicated that SNV induced increases in cGMP (two-threefold) in these cultures, whereas VIP was 1000-fold less potent. These results implicate cGMP as a second messenger for VIP/SNV-mediated effects on neuronal survival. (C) 1999 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:629 / 633
页数:5
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