title: Glucagon-like peptides 1 and 2 and vasoactive intestinal peptide are neuroprotective on cultured and mast cell co-cultured rat myenteric neurons.
abstract: BACKGROUND
  Neuropathy is believed to be a common feature of functional and inflammatory intestinal diseases. Vasoactive intestinal peptide (VIP) is an acknowledged neuroprotective agent in peripheral, including enteric, and central neurons. The proglucagon-like hormones glucagon-like peptide 1 and 2 (GLP1 and GLP2) belong to the secretin/glucagon/VIP superfamily of peptides and GLP1 and GLP2 receptors are expressed in enteric neurons. Possible neuroprotective effects of these peptides were investigated in the present study.
  
  
  METHODS
  GLP1, GLP2 and VIP were added to cultured myenteric neurons from rat small intestine or to co-cultures of myenteric neurons and rat peritoneal mast cells. Receptor selectivity was tested by the simultaneous presence of a GLP1 receptor antagonist (exendin (9-39) amide) or a VIP receptor antagonist (hybrid of neurotensin 6-11 and VIP 7-28). Neuronal survival was examined using immunocytochemistry and cell counting.
  
  
  RESULTS
  GLP1, GLP2 and VIP significantly and concentration-dependently enhanced neuronal survival. In addition the peptides efficiently counteracted mast cell-induced neuronal cell death in a concentration-dependent manner. Exendin(9-39)amide reversed GLP1-induced neuroprotection while GLP2- and VIP-induced enhanced neuronal survival were unaffected. The VIP receptor antagonist reversed GLP1- and VIP-induced neuroprotection while the GLP2-induced effect on neuronal survival was unaffected.
  
  
  CONCLUSIONS
  By activating separate receptors VIP, GLP1 and GLP2 elicit neuroprotective effects on rat myenteric neurons cultured with or without mast cells. This implies a powerful therapeutic potential of these peptides in enteric neuropathies with a broad spectrum of applications from autoimmunity to functional disorders.
authors.affiliation: Department of Experimental Medical Science, BMC B11, Lund University, SE-22184 Lund, Sweden.
authors.forename: Ulrikke
authors.initials: U
authors.lastname: Voss
authors.forename: Elin
authors.initials: E
authors.lastname: Sand
authors.forename: Per M
authors.initials: PM
authors.lastname: Hellström
authors.forename: Eva
authors.initials: E
authors.lastname: Ekblad
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D053767:Glucagon-Like Peptide 2 / Q000494:pharmacology*; D007421:Intestine, Small / Q000294:innervation; D008407:Mast Cells; D009197:Myenteric Plexus; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009496:Neurotensin / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
chemical_list: D053767:Glucagon-Like Peptide 2; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C069189:(VIP-neurotensin) hybrid antagonist; D014660:Vasoactive Intestinal Peptide; D009496:Neurotensin; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1