Inhibition of adenylate cyclase activity in the corneal epithelium by anti-inflammatory steroids
Adenylate cyclase activity in bovine corneal epithelial or rat kidney particulate fractions was completely inhibited by clinically employed levels of anti-inflammatory steroids. Dose-response studies using several steroids showed that dexamethasone phosphate was the most potent enzyme inhibitor, fol...
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| Veröffentlicht in: | Experimental eye research 1982-02, Vol.34 (2), p.161-168 |
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| container_end_page | 168 |
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| container_title | Experimental eye research |
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| creator | Walkenbach, Ronald J. LeGrand, Roy D. |
| description | Adenylate cyclase activity in bovine corneal epithelial or rat kidney particulate fractions was completely inhibited by clinically employed levels of anti-inflammatory steroids. Dose-response studies using several steroids showed that dexamethasone phosphate was the most potent enzyme inhibitor, followed respectively by prednisolone phosphate and hydrocortisone phosphate. Enzyme inhibition occurred regardless of the level or mechanism of adenylate cyclase activation, although agonist-stimulated activity was more sensitive to inhibition than fluoride-stimulated activity. Steroids appear to cause a direct, reversible and non-competitive inhibition of adenylate cyclase, affecting both the apparent substrate affinity and maximum velocity of the enzyme. Application of high levels of anti-inflammatory steroids may block the reported cyclic AMP-mediated effects of increased epithelial wound closure rates and stimulated epithelial basement membrane protein synthesis in a healing cornea. |
| doi_str_mv | 10.1016/0014-4835(82)90050-1 |
| format | Article |
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Dose-response studies using several steroids showed that dexamethasone phosphate was the most potent enzyme inhibitor, followed respectively by prednisolone phosphate and hydrocortisone phosphate. Enzyme inhibition occurred regardless of the level or mechanism of adenylate cyclase activation, although agonist-stimulated activity was more sensitive to inhibition than fluoride-stimulated activity. Steroids appear to cause a direct, reversible and non-competitive inhibition of adenylate cyclase, affecting both the apparent substrate affinity and maximum velocity of the enzyme. Application of high levels of anti-inflammatory steroids may block the reported cyclic AMP-mediated effects of increased epithelial wound closure rates and stimulated epithelial basement membrane protein synthesis in a healing cornea.</description><identifier>ISSN: 0014-4835</identifier><identifier>EISSN: 1096-0007</identifier><identifier>DOI: 10.1016/0014-4835(82)90050-1</identifier><identifier>PMID: 6277681</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>adenylate cyclase ; Adenylyl Cyclase Inhibitors ; Animals ; anti-inflammatory steroids ; Cattle ; cornea ; Cornea - enzymology ; cyclic AMP ; Cyclic AMP - biosynthesis ; Dexamethasone - analogs & derivatives ; Dexamethasone - pharmacology ; Dose-Response Relationship, Drug ; glucocorticoids ; Glucocorticoids - pharmacology ; Hydrocortisone - pharmacology ; Isoproterenol - pharmacology ; Kidney - enzymology ; Prednisolone - analogs & derivatives ; Prednisolone - pharmacology ; Rats</subject><ispartof>Experimental eye research, 1982-02, Vol.34 (2), p.161-168</ispartof><rights>1982</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c357t-26b166bf88e104819dc318e789e682344e923bfe6ac7e8b6ef3a687bc49c2d243</citedby><cites>FETCH-LOGICAL-c357t-26b166bf88e104819dc318e789e682344e923bfe6ac7e8b6ef3a687bc49c2d243</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/0014483582900501$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/6277681$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Walkenbach, Ronald J.</creatorcontrib><creatorcontrib>LeGrand, Roy D.</creatorcontrib><title>Inhibition of adenylate cyclase activity in the corneal epithelium by anti-inflammatory steroids</title><title>Experimental eye research</title><addtitle>Exp Eye Res</addtitle><description>Adenylate cyclase activity in bovine corneal epithelial or rat kidney particulate fractions was completely inhibited by clinically employed levels of anti-inflammatory steroids. Dose-response studies using several steroids showed that dexamethasone phosphate was the most potent enzyme inhibitor, followed respectively by prednisolone phosphate and hydrocortisone phosphate. Enzyme inhibition occurred regardless of the level or mechanism of adenylate cyclase activation, although agonist-stimulated activity was more sensitive to inhibition than fluoride-stimulated activity. Steroids appear to cause a direct, reversible and non-competitive inhibition of adenylate cyclase, affecting both the apparent substrate affinity and maximum velocity of the enzyme. Application of high levels of anti-inflammatory steroids may block the reported cyclic AMP-mediated effects of increased epithelial wound closure rates and stimulated epithelial basement membrane protein synthesis in a healing cornea.</description><subject>adenylate cyclase</subject><subject>Adenylyl Cyclase Inhibitors</subject><subject>Animals</subject><subject>anti-inflammatory steroids</subject><subject>Cattle</subject><subject>cornea</subject><subject>Cornea - enzymology</subject><subject>cyclic AMP</subject><subject>Cyclic AMP - biosynthesis</subject><subject>Dexamethasone - analogs & derivatives</subject><subject>Dexamethasone - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>glucocorticoids</subject><subject>Glucocorticoids - pharmacology</subject><subject>Hydrocortisone - pharmacology</subject><subject>Isoproterenol - pharmacology</subject><subject>Kidney - enzymology</subject><subject>Prednisolone - analogs & derivatives</subject><subject>Prednisolone - pharmacology</subject><subject>Rats</subject><issn>0014-4835</issn><issn>1096-0007</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1982</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE9r3DAQxUVISTebfIMGdArNwa1kaSX5EgihfxYWemnPiiyPyQRb2kpywN--3u6SY07DvHnzhvkR8omzL5xx9ZUxLitpxOazqe8axjas4mdkxVmjKsaYPierN8tHcpnzy6IKqeUFuVC11srwFXnahmdssWAMNPbUdRDmwRWgfvaDy0CdL_iKZaYYaHle9JgCuIHCHpd2wGmk7UxdKFhh6Ac3jq7ENNNcIEXs8hX50Lshw_Wprsmf799-P_6sdr9-bB8fdpUXG12qWrVcqbY3BjiThjedF9yANg0oUwspoalF24NyXoNpFfTCKaNbLxtfd7UUa3J7zN2n-HeCXOyI2cMwuABxylaLRmst2WKUR6NPMecEvd0nHF2aLWf2ANYeqNkDNWtq-x-s5cvazSl_akfo3pZOJJf5_XEOy5OvCMlmjxA8dJjAF9tFfP_AP8XTiKQ</recordid><startdate>198202</startdate><enddate>198202</enddate><creator>Walkenbach, Ronald J.</creator><creator>LeGrand, Roy D.</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>198202</creationdate><title>Inhibition of adenylate cyclase activity in the corneal epithelium by anti-inflammatory steroids</title><author>Walkenbach, Ronald J. ; LeGrand, Roy D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c357t-26b166bf88e104819dc318e789e682344e923bfe6ac7e8b6ef3a687bc49c2d243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1982</creationdate><topic>adenylate cyclase</topic><topic>Adenylyl Cyclase Inhibitors</topic><topic>Animals</topic><topic>anti-inflammatory steroids</topic><topic>Cattle</topic><topic>cornea</topic><topic>Cornea - enzymology</topic><topic>cyclic AMP</topic><topic>Cyclic AMP - biosynthesis</topic><topic>Dexamethasone - analogs & derivatives</topic><topic>Dexamethasone - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>glucocorticoids</topic><topic>Glucocorticoids - pharmacology</topic><topic>Hydrocortisone - pharmacology</topic><topic>Isoproterenol - pharmacology</topic><topic>Kidney - enzymology</topic><topic>Prednisolone - analogs & derivatives</topic><topic>Prednisolone - pharmacology</topic><topic>Rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Walkenbach, Ronald J.</creatorcontrib><creatorcontrib>LeGrand, Roy D.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental eye research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Walkenbach, Ronald J.</au><au>LeGrand, Roy D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of adenylate cyclase activity in the corneal epithelium by anti-inflammatory steroids</atitle><jtitle>Experimental eye research</jtitle><addtitle>Exp Eye Res</addtitle><date>1982-02</date><risdate>1982</risdate><volume>34</volume><issue>2</issue><spage>161</spage><epage>168</epage><pages>161-168</pages><issn>0014-4835</issn><eissn>1096-0007</eissn><abstract>Adenylate cyclase activity in bovine corneal epithelial or rat kidney particulate fractions was completely inhibited by clinically employed levels of anti-inflammatory steroids. Dose-response studies using several steroids showed that dexamethasone phosphate was the most potent enzyme inhibitor, followed respectively by prednisolone phosphate and hydrocortisone phosphate. Enzyme inhibition occurred regardless of the level or mechanism of adenylate cyclase activation, although agonist-stimulated activity was more sensitive to inhibition than fluoride-stimulated activity. Steroids appear to cause a direct, reversible and non-competitive inhibition of adenylate cyclase, affecting both the apparent substrate affinity and maximum velocity of the enzyme. Application of high levels of anti-inflammatory steroids may block the reported cyclic AMP-mediated effects of increased epithelial wound closure rates and stimulated epithelial basement membrane protein synthesis in a healing cornea.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>6277681</pmid><doi>10.1016/0014-4835(82)90050-1</doi><tpages>8</tpages></addata></record> |
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| ispartof | Experimental eye research, 1982-02, Vol.34 (2), p.161-168 |
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| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | adenylate cyclase Adenylyl Cyclase Inhibitors Animals anti-inflammatory steroids Cattle cornea Cornea - enzymology cyclic AMP Cyclic AMP - biosynthesis Dexamethasone - analogs & derivatives Dexamethasone - pharmacology Dose-Response Relationship, Drug glucocorticoids Glucocorticoids - pharmacology Hydrocortisone - pharmacology Isoproterenol - pharmacology Kidney - enzymology Prednisolone - analogs & derivatives Prednisolone - pharmacology Rats |
| title | Inhibition of adenylate cyclase activity in the corneal epithelium by anti-inflammatory steroids |
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