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

The current study explored whether the neuroprotective effects of vasoactiv e intestinal peptide (VIP) and its analog Stearyl-Nle(17)-VIP (SNV) were me diated through cGMP. SNV, was previously found to be 100-fold more potent t han 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 neu roprotection against 10(-12) M of the cGMP antagonist. Immunoassays indicat ed that SNV induced increases in cGMP (two-threefold) in these cultures, wh ereas VIP was 1000-fold less potent. These results implicate cGMP as a seco nd messenger for VIP/SNV-mediated effects on neuronal survival. (C) 1999 El sevier Science Inc. All rights reserved.