D1-type dopamine receptors inhibit growth cone motility in cultured retina neurons: evidence that neurotransmitters act as morphogenic growth regulators in the developing central nervous system

Proc Natl Acad Sci U S A. 1988 Apr;85(8):2839-43. doi: 10.1073/pnas.85.8.2839.

Abstract

Precedent exists for the early development and subsequent down-regulation of neurotransmitter receptor systems in the vertebrate central nervous system, but the function of such embryonic receptors has not been established. Here we show that stimulation of early-developing dopamine receptors in avian retina cells greatly inhibits the motility of neuronal growth cones. Neurons from embryonic chicken retinas were cultured in low-density monolayers, and their growth cones were observed with phase-contrast or video-enhanced-contrast-differential-interference-contrast (VEC-DIC) microscopy. Approximately 25% of the neurons responded to micromolar dopamine with a rapid reduction in filopodial activity followed by a flattening of growth cones and retraction of neurites. The response occurred at all ages examined (embryonic day-8 retinal neurons cultured on polylysine-coated coverslips for 1-7 days), although neurite retraction was greatest in younger cultures. Effects of dopamine on growth cone function could be reversed by haloperidol or (+)-SCH 23390, whereas forskolin elicited a response similar to dopamine; these data show the response was receptor-mediated, acting through a D1-type system, and are consistent with the use of cAMP as a second messenger. The experiments provide strong support for the hypothesis that neurotransmitters, besides mediating transynaptic signaling in the adult, may have a role in neuronal differentiation as growth regulators.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Chick Embryo
  • Colforsin / pharmacology
  • Dopamine / pharmacology*
  • Dopamine Antagonists
  • Growth Inhibitors*
  • Morphogenesis*
  • Receptors, Dopamine / physiology*
  • Retina / cytology
  • Retina / growth & development*

Substances

  • Dopamine Antagonists
  • Growth Inhibitors
  • Receptors, Dopamine
  • Colforsin
  • Adenylyl Cyclases
  • Dopamine