Vasoactive intestinal peptide and related molecules induce nitrite accumulation in the extracellular milieu of rat cerebral cortical cultures

• Published in: Neuroscience letters Vol. 307; no. 3; pp. 167 - 170
• Main Authors: Ashur-Fabian, Osnat, Giladi, Eliezer, Furman, Sharon, Steingart, Ruth A, Wollman, Yoram, Fridkin, Mati, Brenneman, Douglas E, Gozes, Illana
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 20.07.2001; Elsevier
• Subjects: Activity-dependent neuroprotective protein; Animals; Animals, Newborn; Biochemistry and metabolism; Biological and medical sciences; Cells, Cultured - cytology; Cells, Cultured - drug effects; Cells, Cultured - metabolism; Central nervous system; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cortical cultures; Cyclic GMP - metabolism; Cyclic guanosine monophosphate; Dose-Response Relationship, Drug; Extracellular Space - drug effects; Extracellular Space - metabolism; Fundamental and applied biological sciences. Psychology; Neuroglia - cytology; Neuroglia - drug effects; Neuroglia - metabolism; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Neuroprotective Agents - pharmacology; Nitric Oxide; Nitric Oxide - metabolism; Nitrites - metabolism; Oligopeptides - pharmacology; Rats; Stearyl-norleucine17-Vasoactive intestinal peptide; Vasoactive intestinal peptide; Vasoactive Intestinal Peptide - pharmacology; Vertebrates: nervous system and sense organs; Activity-dependent neuroprotective protein; Nitric Oxide; Vasoactive intestinal peptide; Stearyl-norleucine17-Vasoactive intestinal peptide; Cyclic guanosine monophosphate; Cortical cultures; Cerebral cortex; Rat; Nitrites; Rodentia; Central nervous system; 3',5'-GMP; Extracellular; In vitro; Vertebrata; Mammalia; Analog; Nitric oxide; Biological accumulation; Brain (vertebrata)
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(01)01954-1

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.