title: The cyclic AMP effects and neuroprotective activities of PACAP and VIP in cultured astrocytes and neurons exposed to oxygen-glucose deprivation.
abstract: BACKGROUND
  Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are endogenous peptides, widely expressed in the central and peripheral nervous system. The adenylyl cyclase (AC)/cyclic AMP (cAMP) is their main intracellular signal transduction pathway. Numerous data suggest that PACAP and VIP have considerable neuroprotective potential, indicating the possibility for their use as new therapeutic strategies in stroke treatment. The aim of this study was to evaluate the effect of oxygen-glucose deprivation (OGD) - an established in vitro model for ischemic cell stress - on PACAP and VIP-evoked receptor-mediated cAMP generation in glial and neuronal cells, and to determine whether PACAP and VIP have neuroprotective activity under these conditions.
  
  
  METHODS
  The formation of [(3)H]cAMP by PACAP, VIP and forskolin (a direct activator of AC) was measured in [(3)H]adenine prelabeled primary rat glial and neuronal cells under normoxia and OGD conditions. The effects of PACAP and VIP on cell viability were measured using the MTT conversion method, and were compared to tacrolimus (FK506), a well known neuroprotective agent.
  
  
  RESULTS
  The OGD model inhibited the PACAP and VIP-induced cAMP formation in rat astrocytes and neurons. Incubation of neuronal cells with PACAP prevented OGD-induced cell death, more efficiently than VIP and FK506.
  
  
  CONCLUSIONS
  The obtained results showed that hypoxia/ischemia may trigger down-regulation of the brain AC-coupled PACAP/VIP receptors, with a consequent decrease of PACAP- and/or VIP-ergic-dependent cAMP-driven signaling. Moreover, our findings indicate that PACAP and VIP can prevent the deleterious effect of OGD on rat neuronal cells.
authors.affiliation: Department of Pharmacology and Toxicology, The Interfaculty Chair of Basic and Clinical Pharmacology, Medical University of Lodz, Łódź, Poland. Electronic address: marta.jozwiak-bebenista@umed.lodz.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Jóźwiak-Bębenista
authors.affiliation: Department of Pharmacology and Toxicology, The Interfaculty Chair of Basic and Clinical Pharmacology, Medical University of Lodz, Łódź, Poland.
authors.forename: Edward
authors.initials: E
authors.lastname: Kowalczyk
authors.affiliation: Department of Pharmacology and Toxicology, The Interfaculty Chair of Basic and Clinical Pharmacology, Medical University of Lodz, Łódź, Poland.
authors.forename: Jerzy Z
authors.initials: JZ
authors.lastname: Nowak
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D003035:Cobalt; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D005947:Glucose / Q000172:deficiency* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D061251:Primary Cell Culture; D051381:Rats; D016559:Tacrolimus / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D003035:Cobalt; D000242:Cyclic AMP; C018021:cobaltous chloride; D005947:Glucose; D010100:Oxygen; D016559:Tacrolimus
keywords: Hypoxia; Neuroprotection; Oxygen-glucose deprivation (OGD); Pituitary adenylate cyclase-activating polypeptide (PACAP); Vasoactive intestinal peptide (VIP)