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Article: Regulation of cyclic GMP metabolism in toad photoreceptors. Definition of the metabolic events subserving photoexcited and attenuated states

TitleRegulation of cyclic GMP metabolism in toad photoreceptors. Definition of the metabolic events subserving photoexcited and attenuated states
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date1988
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 1988, v. 263 n. 18, p. 8771-8785 How to Cite?
AbstractPhotoreceptor metabolism of cGMP and its regulation were characterized in isolated toad retinas by determining the intensity and time dependence of light-induced changes in the following metabolic parameters: cGMP hydrolytic flux determined by the rate of 18O incorporation from 18O-water into retinal guanine nucleotide α-phosphoryls; changes in the total (protein-bound and unbound) concentrations of the guanine nucletodie metabolic intermediates; and changes in the concentration of metabolic (unbound) GDP calculated from the fraction of the α-GDP that undergoes labeling with 18O. The latter is interpreted to reflect the state of the equilibrium between GDP-GTP-complexed forms of G-protein. With narrow band 500 nm light that preferentially stimulates ared rod photoreceptors, a range of intensities covering approximately 5 log units produced increases of over 10-fold in cGMP metabolic flux. However, the characteristics of the cGMP metabolic response over the first 2.5 log units of intensity are readily distinguishable from those at higher intensities which exhibit progressive attenuation by an intensity- and time-dependent process. Over the range of low intensities (0.6-3 log photons·μm-2·s-1) the metabolic response is characterized by 1) increases in cGMP hydrolytic flux of up to 8-fold as a logarithmic function of intensity of photic stimulation that are sustained for at least 200 s; 2) small increases or no change in the concentration of total cGMP; 3) large increases of up to 10-fold in the concentration of metabolically active GDP as a linear function of intensity with no significant change in the tissue concentrations of total GDP or GTP; and 4) amplification of the photosignal by the metabolism of approximately 10,000 molecules of cGMP per photoisomerization with the major site of amplification at the level of the interaction of bleached rhodopsin with G-protein. The attenuated cGMP hydrolytic response observed in a high light intensity range (3-5.39 log photons·μm-2·s-1) exhibits the following characteristics: 1) a progressive decline in the magnitude of the light-accelerated cGMP hydrolytic flux response with respect to the photon flux which at the highest intensities leads to relative declines in the cGMP flux after 20 s of illumination and more pronounced decreases after 200 s of illumination; 2) progressive decreases of as much as 25% at 20 s and up to 50% at 200 s in the total cGMP concentration that are proportional to the suppression observed in light-enhanced cGMP hydrolytic flux; and 3) decreases from the maximal levels achieved in the concentration of metabolic (unbound) GDP with no change in total GDP or GTP concentration. The widely held view of a light-activated cascade directed only toward phosphodiesterase cannot account for any of the above features of cGMP metabolism in the intact photoreceptor. To sustain a cGMP flux that is severalfold greater than that in the dark-adapted state, continuous illumination must activate the entire cGMP metabolic cycle, which consists of phosphodiesterase, guanylyl cyclase, and the enzymes phosphorylating GMP and GDP. This mechanism is also consistent with the observation that concentrations of cGMP, GDP, and GTP remain nearly constant during low intensity photic stimulation. To produce the time-dependent attenuation in light-activated flux with the accompanying reductions in total cGMP concentration, intense and extended illumination must result in a gradual down-regulation of light-activated guanylyl cyclase. This perspective contradicts the currently held view of the mechanisim, outcome, and purpose of light-induced alterations in cGMP metabolism.
Persistent Identifierhttp://hdl.handle.net/10722/132589
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorDawis, SMen_HK
dc.contributor.authorGraeff, RMen_HK
dc.contributor.authorHeyman, RAen_HK
dc.contributor.authorWalseth, TFen_HK
dc.contributor.authorGoldberg, NDen_HK
dc.date.accessioned2011-03-28T09:26:34Z-
dc.date.available2011-03-28T09:26:34Z-
dc.date.issued1988en_HK
dc.identifier.citationJournal Of Biological Chemistry, 1988, v. 263 n. 18, p. 8771-8785en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/132589-
dc.description.abstractPhotoreceptor metabolism of cGMP and its regulation were characterized in isolated toad retinas by determining the intensity and time dependence of light-induced changes in the following metabolic parameters: cGMP hydrolytic flux determined by the rate of 18O incorporation from 18O-water into retinal guanine nucleotide α-phosphoryls; changes in the total (protein-bound and unbound) concentrations of the guanine nucletodie metabolic intermediates; and changes in the concentration of metabolic (unbound) GDP calculated from the fraction of the α-GDP that undergoes labeling with 18O. The latter is interpreted to reflect the state of the equilibrium between GDP-GTP-complexed forms of G-protein. With narrow band 500 nm light that preferentially stimulates ared rod photoreceptors, a range of intensities covering approximately 5 log units produced increases of over 10-fold in cGMP metabolic flux. However, the characteristics of the cGMP metabolic response over the first 2.5 log units of intensity are readily distinguishable from those at higher intensities which exhibit progressive attenuation by an intensity- and time-dependent process. Over the range of low intensities (0.6-3 log photons·μm-2·s-1) the metabolic response is characterized by 1) increases in cGMP hydrolytic flux of up to 8-fold as a logarithmic function of intensity of photic stimulation that are sustained for at least 200 s; 2) small increases or no change in the concentration of total cGMP; 3) large increases of up to 10-fold in the concentration of metabolically active GDP as a linear function of intensity with no significant change in the tissue concentrations of total GDP or GTP; and 4) amplification of the photosignal by the metabolism of approximately 10,000 molecules of cGMP per photoisomerization with the major site of amplification at the level of the interaction of bleached rhodopsin with G-protein. The attenuated cGMP hydrolytic response observed in a high light intensity range (3-5.39 log photons·μm-2·s-1) exhibits the following characteristics: 1) a progressive decline in the magnitude of the light-accelerated cGMP hydrolytic flux response with respect to the photon flux which at the highest intensities leads to relative declines in the cGMP flux after 20 s of illumination and more pronounced decreases after 200 s of illumination; 2) progressive decreases of as much as 25% at 20 s and up to 50% at 200 s in the total cGMP concentration that are proportional to the suppression observed in light-enhanced cGMP hydrolytic flux; and 3) decreases from the maximal levels achieved in the concentration of metabolic (unbound) GDP with no change in total GDP or GTP concentration. The widely held view of a light-activated cascade directed only toward phosphodiesterase cannot account for any of the above features of cGMP metabolism in the intact photoreceptor. To sustain a cGMP flux that is severalfold greater than that in the dark-adapted state, continuous illumination must activate the entire cGMP metabolic cycle, which consists of phosphodiesterase, guanylyl cyclase, and the enzymes phosphorylating GMP and GDP. This mechanism is also consistent with the observation that concentrations of cGMP, GDP, and GTP remain nearly constant during low intensity photic stimulation. To produce the time-dependent attenuation in light-activated flux with the accompanying reductions in total cGMP concentration, intense and extended illumination must result in a gradual down-regulation of light-activated guanylyl cyclase. This perspective contradicts the currently held view of the mechanisim, outcome, and purpose of light-induced alterations in cGMP metabolism.en_HK
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.subjectChemicals And Cas Registry Numbersen_US
dc.titleRegulation of cyclic GMP metabolism in toad photoreceptors. Definition of the metabolic events subserving photoexcited and attenuated statesen_HK
dc.typeArticleen_HK
dc.identifier.emailGraeff, RM: graeffr@hku.hken_HK
dc.identifier.authorityGraeff, RM=rp01464en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid2837463-
dc.identifier.scopuseid_2-s2.0-0023902409en_HK
dc.identifier.volume263en_HK
dc.identifier.issue18en_HK
dc.identifier.spage8771en_HK
dc.identifier.epage8785en_HK
dc.identifier.isiWOS:A1988N925700036-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridDawis, SM=6602520296en_HK
dc.identifier.scopusauthoridGraeff, RM=7003614053en_HK
dc.identifier.scopusauthoridHeyman, RA=35599662900en_HK
dc.identifier.scopusauthoridWalseth, TF=7005424273en_HK
dc.identifier.scopusauthoridGoldberg, ND=23085828700en_HK

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