Differences in the pharmacological activation of visual opsins

Vis Neurosci. 2006 Nov-Dec;23(6):899-908. doi: 10.1017/S0952523806230256.

Abstract

Opsins, like many other G-protein-coupled receptors, sustain constitutive activity in the absence of ligand. In partially bleached rods and cones, opsin's activity closes cGMP-gated channels and produces a state of "pigment adaptation" with reduced sensitivity to light and accelerated flash response kinetics. The truncated retinal analogue, beta-ionone, further desensitizes partially bleached green-sensitive salamander rods, but enables partially bleached red-sensitive cones to recover dark-adapted physiology. Structural differences between rod and cone opsins were proposed to explain the effect. Rods and cones, however, also contain different transducins, raising the possibility that G-protein type determines the photoreceptor-specific effects of beta-ionone. To test the two hypotheses, we applied beta-ionone to partially bleached blue-sensitive rods and cones of salamander, two cells that couple the same cone-like opsin to either rod or cone transducin, respectively. Immunocytochemistry confirmed that all salamander rods contain one form of transducin, whereas all cones contain another. beta-Ionone enhanced pigment adaptation in blue-sensitive rods, but it also did so in blue- and UV-sensitive cones. Furthermore, all recombinant salamander rod and cone opsins, with the exception of the red-sensitive cone opsin, activated rod transducin upon the addition of beta-ionone. Thus opsin structure determines the identity of beta-ionone as an agonist or an inverse agonist and in that respect distinguishes the red-sensitive cone opsin from all others.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Cricetinae
  • Dark Adaptation
  • Enzyme Activation / drug effects
  • Larva
  • Membrane Potentials / drug effects
  • Membrane Potentials / radiation effects
  • Norisoprenoids / pharmacology*
  • Photic Stimulation
  • Retina / cytology
  • Retinal Cone Photoreceptor Cells / drug effects*
  • Retinal Cone Photoreceptor Cells / metabolism
  • Retinal Rod Photoreceptor Cells / drug effects*
  • Retinal Rod Photoreceptor Cells / metabolism
  • Rod Opsins / metabolism*
  • Transducin / metabolism
  • Urodela

Substances

  • Norisoprenoids
  • Rod Opsins
  • beta-ionone
  • Transducin