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.
Isayama
T
T
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA. tomoki_isayama@meei.harvard.edu
Chen
Y
Y
Kono
M
M
Degrip
W J
WJ
Ma
J-X
JX
Crouch
R K
RK
Makino
C L
CL
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003623:Dark Adaptation; D004789:Enzyme Activation / Q000187:drug effects; D007814:Larva; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D045792:Norisoprenoids / Q000494:pharmacology*; D010775:Photic Stimulation; D012160:Retina / Q000166:cytology; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects* / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects* / Q000378:metabolism; D017299:Rod Opsins / Q000378:metabolism*; D015293:Transducin / Q000378:metabolism; D014562:Caudata
D045792:Norisoprenoids; D017299:Rod Opsins; C008157:beta-ionone; D015293:Transducin