The current study explored whether the neuroprotective effects of vasoactive intestinal peptide (VIP) and its analog Stearyl-Nle17-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 cortical 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. Copyright (C) 1999 Elsevier Science Inc.
- Cyclic guanosine monophosphate (cGMP)
- Enzymeimmunoassays (EIA)
- Neuronal survival
- Radioimmunoassays (RIA)
- Stearyl-Nle-VIP (SNV)
- Vasoactive intestinal peptide (VIP)