Vasoactive intestinal peptide and related molecules induce nitrite accumulation in the extracellular milieu of rat cerebral cortical cultures.
Nanomolar concentrations of vasoactive intestinal peptide (VIP), picomolar concentrations of stearyl-norleucine17-VIP (SNV) and femtomolar concentrations of NAPVSIPQ (NAP), an 8-amino-acid peptide derived from the VIP-responsive activity-dependent neuroprotective protein, provide broad neuroprotection. In rat cerebral cortical cultures, 10(-16)-10(-7) M NAP increased intracellular cyclic guanosine monophosphate (cGMP) (2.5-4-fold) and 10(-10) M NAP increased extracellular nitric oxide (NO) by 60%. In the same culture system, VIP and SNV (at micromolar concentrations) increased extracellular NO by 45-55%. The NAP dose required for cGMP increases correlated with the dose providing neuroprotection. However, the concentrations of NAP, SNV and VIP affecting NO production did not match the neuro-protective doses. Thus, NO may mediate part of the cell-cell interaction and natural maintenance activity of VIP/SNV/NAP, while cGMP may mediate neuroprotection.
Ashur-Fabian
O
O
Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel
Giladi
E
E
Furman
S
S
Steingart
R A
RA
Wollman
Y
Y
Fridkin
M
M
Brenneman
D E
DE
Gozes
I
I
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects* / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D018696:Neuroprotective Agents; D009573:Nitrites; D009842:Oligopeptides; C086770:stearyl-norleucine(17)-vasoactive intestinal peptide; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; C425904:davunetide; D006152:Cyclic GMP