The described projects deal with the structure, function and metabolism of specific retinal cells involved in the processing of visual information. O r current interest is in how light and also molecules acting at surface receptors of photoreceptors modify their biochemistry and physiology. We will continue to study the kinetics of light dependent nucleotide metabolis in outer segments of amphibian photoreceptors. This project involves illuminating retinas for known brief intervals, ultrarapid-freezing of thei outer segment surface, and obtaining sections of frozen outer segments for cGMP assay. The new projects concern the levels of cGMP, GTP, and GDP in O as a function of the adaptive state of the receptor, including conditions where the medium has different buffered calcium levels.
One aim i s to help characterize the modulation of cyclase activity in the intact photoreceptor A second project focuses on membrane receptors which can modulate light- sensitive cAMP in dark adapted photoreceptors. Tryptamine, serotonin, and a purported dopamine D2 agonist, LY 17155, eliminate this pool when applied in the dark. We plan to further characterize the receptors, to localize th receptors by slide-binding autoradiography, and as a function of the diurna cycle to quantify endogenous ligands that may regulate this cAMP pool. A third project relates to the high taurine content of photoreceptors, a molecule whose deficiency causes loss or damage of these cells, particularl cones. Hypotheses for taurine function in photoreceptors have included osmoregulation and membrane stabilization. In addition, investigations of cardiac muscle and adipose tissue have called attention to the interaction of receptors. As such hypotheses for the function of this molecule require some interaction of taurine with membrane or channel proteins, we plan to identify and characterize bovine retinal and/or photoreceptoral proteins which bind taurine, to investigate any relation to insulin receptors, with the long range aim of isolating and inserting such protein(s) in artificial membrane vesicles to help address their function. Investigations on the details of photoreceptor structure and biochemistry are particularly important in view of the many types of blindness apparently based on defect of an eventual loss of these cells.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY000258-28
Application #
3255224
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1979-09-01
Project End
1994-08-31
Budget Start
1990-09-01
Budget End
1991-08-31
Support Year
28
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Cohen, A I; Blazynski, C (1993) The determination of total cGMP levels in rod outer segments from intact toad photoreceptors in response to light superimposed on background and to consecutive flashes: a second light flash accelerates the dark recovery rate of cGMP levels in control medi Vis Neurosci 10:73-9
Cohen, A I; Todd, R D; Harmon, S et al. (1992) Photoreceptors of mouse retinas possess D4 receptors coupled to adenylate cyclase. Proc Natl Acad Sci U S A 89:12093-7
Blazynski, C; Perez, M T (1991) Adenosine in vertebrate retina: localization, receptor characterization, and function. Cell Mol Neurobiol 11:463-84
Blazynski, C (1991) The accumulation of [3H]phenylisopropyl adenosine ([3H]PIA) and [3H]adenosine into rabbit retinal neurons is inhibited by nitrobenzylthioinosine (NBI). Neurosci Lett 121:1-4
Blazynski, C; Dubocovich, M L (1991) Localization of 2-[125I]iodomelatonin binding sites in mammalian retina. J Neurochem 56:1873-80
Blazynski, C (1990) Discrete distributions of adenosine receptors in mammalian retina. J Neurochem 54:648-55
Cohen, A I; Blazynski, C (1990) Dopamine and its agonists reduce a light-sensitive pool of cyclic AMP in mouse photoreceptors. Vis Neurosci 4:43-52
Blazynski, C; Mosinger, J L; Cohen, A I (1989) Comparison of adenosine uptake and endogenous adenosine-containing cells in mammalian retina. Vis Neurosci 2:109-16
Cohen, A I; Blazynski, C (1988) Light-induced losses and dark recovery rates of guanosine 3',5'-cyclic monophosphate in rod outer segments of intact amphibian photoreceptors. J Gen Physiol 92:731-46
Brown, J E; Blazynski, C; Cohen, A I (1987) Light induces a rapid and transient increase in inositol-trisphosphate in toad rod outer segments. Biochem Biophys Res Commun 146:1392-6

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