Synergistic effects of substance P with insulin-like growth factor-1 on epithelial migration of the cornea

J Cell Physiol. 1996 Oct;169(1):159-66. doi: 10.1002/(SICI)1097-4652(199610)169:1<159::AID-JCP16>3.0.CO;2-8.


We find that substance P (SP) and insulin-like growth factor-1 (IGF-1) demonstrate a synergistic effect on the stimulation of rabbit corneal epithelial migration in an organ culture. The addition of either SP or IGF-1 alone did not affect epithelial migration, while the combination of SP and IGF-1 stimulated epithelial migration in a dose-dependent fashion. The synergistic effects of SP and IGF-1 on corneal epithelial migration were nulled by the addition of a SP antagonist or enkephalinase. Among neurotransmitters (vasoactive intestinal peptide, calcitonin gene-related peptide, acethylcholine chloride, norepinephrine, serotonin) or tachykinins (neurokinin A, neurokinin B, kassinin, eledoisin, physalaemin), only SP demonstrated a synergistic effect with IGF-1 on cellular migration. In contrast, the combination of SP and IGF-1 did not affect the incorporation of 3H-thymidine into corneal epithelial cells. The attachment of the corneal epithelial cells to fibronectin, collagen type IV, and laminin matrices increased after treatment of the cells with SP and IGF-1, but SP or IGF-1 by themselves did not affect the attachment of the cells to these extracellular matrix proteins. An identical synergistic effect on corneal epithelial migration was observed when an NK-1 receptor agonist was used in place of SP, suggesting the synergistic effect of SP and IGF-1 might be mediated through the NK-1 receptor system. These results suggest that the maintenance of the normal integrity of the corneal epithelium might be regulated by both humoral and neural factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Cornea / cytology
  • Cornea / drug effects*
  • Cornea / physiology*
  • Drug Synergism
  • Epithelial Cells
  • Epithelium / drug effects
  • Epithelium / physiology
  • Extracellular Matrix Proteins / pharmacology
  • Insulin-Like Growth Factor I / pharmacology*
  • Neprilysin / pharmacology
  • Neuropeptides / pharmacology
  • Organ Culture Techniques
  • Rabbits
  • Receptors, Neurokinin-1 / agonists
  • Substance P / analogs & derivatives
  • Substance P / pharmacology*
  • Thymidine / metabolism


  • Extracellular Matrix Proteins
  • Neuropeptides
  • Receptors, Neurokinin-1
  • Substance P
  • Insulin-Like Growth Factor I
  • Neprilysin
  • Thymidine