Differences in the pharmacological activation of visual opsins
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.(Received June 23 2006)
(Accepted September 29 2006)
Key Words: Rod; Cone; Rhodopsin; Transducin; Phototransduction.
c1 Address correspondence and reprint requests to: Tomoki Isayama, Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, 243 Charles Street, Boston, MA 02114. E-mail: firstname.lastname@example.org