Contributions of Adenosine Receptor Activation to the Ocular Actions of Epinephrine
Epinephrine is an effective drug for glaucoma treatment. However, the mechanisms responsible for the ocular hypotensive action of this compound are not completely understood. Adenosine is an autacoid released by all cells. This study evaluated the role of adenosine receptor activation in epinephrine...
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| Veröffentlicht in: | Investigative ophthalmology & visual science 1999-08, Vol.40 (9), p.2054-2061 |
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| description | Epinephrine is an effective drug for glaucoma treatment. However, the mechanisms responsible for the ocular hypotensive action of this compound are not completely understood. Adenosine is an autacoid released by all cells. This study evaluated the role of adenosine receptor activation in epinephrine-induced changes in ocular function.
Rabbits were pretreated topically with the moderately selective adenosine A1 antagonist 8-(p-sulfophenyl)theophylline (8-SPT) or the adenosine A2 antagonist 3,7-dimethyl-l-propargylxanthine (DMPX). Epinephrine (500 microg) was then administered, and intraocular pressures (IOPs), pupil diameters (PDs), or total outflow facility was evaluated. In a separate group of animals, epinephrine or vehicle was administered, and aqueous humor samples obtained to evaluate changes in aqueous humor purine levels by means of high-performance liquid chromatography.
In control animals, epinephrine produced a biphasic change in IOP: an initial rise in IOP of approximately 1 mm Hg from 1/2 to 1 hour followed by significant reduction in IOP of 8 to 9 mm Hg from 3 to 5 hours postadministration. These animals also exhibited a significant increase in PD of 2 to 3 mm from 1/2 to 2 hours postadministration. Pretreatment with 8-SPT (1000 microg) enhanced the initial rise in IOP, while significantly inhibiting the ocular hypotensive response. Pretreatment with 8-SPT also significantly enhanced the epinephrine-induced increase in PD. Inhibition of the epinephrine-induced reduction in IOP by 8-SPT was dose-related with an IC50 of 446 microg. Administration of 8-SPT alone did not significantly alter IOP or PD. The A2 antagonist DMPX did not alter the epinephrine-induced change in IOP or PD. In rabbits pretreated with 8-SPT, the epinephrine-induced increase in outflow facility was significantly reduced by 60% when compared with those in rabbits treated with epinephrine alone. In vehicle-treated rabbits, aqueous humor adenosine and inosine levels were 2.7 +/- 0.38 and 29 +/- 4.2 ng/100 microl, respectively. Three hours after epinephrine administration, adenosine and inosine levels had significantly increased to 11 +/- 1.6 and 66 +/- 4.4 ng/100 microl, respectively.
These results support the idea that in rabbits epinephrine administration stimulates adenosine release in the anterior segment. This rise in endogenous levels of adenosine then leads to the activation of ocular adenosine receptors and is in part responsible for the ocular hypotensive action of epi |
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Rabbits were pretreated topically with the moderately selective adenosine A1 antagonist 8-(p-sulfophenyl)theophylline (8-SPT) or the adenosine A2 antagonist 3,7-dimethyl-l-propargylxanthine (DMPX). Epinephrine (500 microg) was then administered, and intraocular pressures (IOPs), pupil diameters (PDs), or total outflow facility was evaluated. In a separate group of animals, epinephrine or vehicle was administered, and aqueous humor samples obtained to evaluate changes in aqueous humor purine levels by means of high-performance liquid chromatography.
In control animals, epinephrine produced a biphasic change in IOP: an initial rise in IOP of approximately 1 mm Hg from 1/2 to 1 hour followed by significant reduction in IOP of 8 to 9 mm Hg from 3 to 5 hours postadministration. These animals also exhibited a significant increase in PD of 2 to 3 mm from 1/2 to 2 hours postadministration. Pretreatment with 8-SPT (1000 microg) enhanced the initial rise in IOP, while significantly inhibiting the ocular hypotensive response. Pretreatment with 8-SPT also significantly enhanced the epinephrine-induced increase in PD. Inhibition of the epinephrine-induced reduction in IOP by 8-SPT was dose-related with an IC50 of 446 microg. Administration of 8-SPT alone did not significantly alter IOP or PD. The A2 antagonist DMPX did not alter the epinephrine-induced change in IOP or PD. In rabbits pretreated with 8-SPT, the epinephrine-induced increase in outflow facility was significantly reduced by 60% when compared with those in rabbits treated with epinephrine alone. In vehicle-treated rabbits, aqueous humor adenosine and inosine levels were 2.7 +/- 0.38 and 29 +/- 4.2 ng/100 microl, respectively. Three hours after epinephrine administration, adenosine and inosine levels had significantly increased to 11 +/- 1.6 and 66 +/- 4.4 ng/100 microl, respectively.
These results support the idea that in rabbits epinephrine administration stimulates adenosine release in the anterior segment. This rise in endogenous levels of adenosine then leads to the activation of ocular adenosine receptors and is in part responsible for the ocular hypotensive action of epinephrine.</description><identifier>ISSN: 0146-0404</identifier><identifier>EISSN: 1552-5783</identifier><identifier>PMID: 10440261</identifier><identifier>CODEN: IOVSDA</identifier><language>eng</language><publisher>Rockville, MD: ARVO</publisher><subject><![CDATA[Adenosine - metabolism ; Adrenergic Agonists - administration & dosage ; Adrenergic Agonists - pharmacology ; Animals ; Aqueous Humor - drug effects ; Aqueous Humor - metabolism ; Biological and medical sciences ; Epinephrine - administration & dosage ; Epinephrine - pharmacology ; Eye ; Inosine - metabolism ; Intraocular Pressure - drug effects ; Medical sciences ; Ophthalmic Solutions - administration & dosage ; Ophthalmic Solutions - pharmacology ; Pharmacology. Drug treatments ; Pupil - drug effects ; Purinergic P1 Receptor Antagonists ; Rabbits ; Receptors, Purinergic P1 - metabolism ; Theobromine - administration & dosage ; Theobromine - analogs & derivatives ; Theobromine - pharmacology ; Theophylline - administration & dosage ; Theophylline - analogs & derivatives ; Theophylline - pharmacology]]></subject><ispartof>Investigative ophthalmology & visual science, 1999-08, Vol.40 (9), p.2054-2061</ispartof><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1923127$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10440261$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Crosson, Craig E</creatorcontrib><creatorcontrib>Petrovich, Margaret</creatorcontrib><title>Contributions of Adenosine Receptor Activation to the Ocular Actions of Epinephrine</title><title>Investigative ophthalmology & visual science</title><addtitle>Invest Ophthalmol Vis Sci</addtitle><description>Epinephrine is an effective drug for glaucoma treatment. However, the mechanisms responsible for the ocular hypotensive action of this compound are not completely understood. Adenosine is an autacoid released by all cells. This study evaluated the role of adenosine receptor activation in epinephrine-induced changes in ocular function.
Rabbits were pretreated topically with the moderately selective adenosine A1 antagonist 8-(p-sulfophenyl)theophylline (8-SPT) or the adenosine A2 antagonist 3,7-dimethyl-l-propargylxanthine (DMPX). Epinephrine (500 microg) was then administered, and intraocular pressures (IOPs), pupil diameters (PDs), or total outflow facility was evaluated. In a separate group of animals, epinephrine or vehicle was administered, and aqueous humor samples obtained to evaluate changes in aqueous humor purine levels by means of high-performance liquid chromatography.
In control animals, epinephrine produced a biphasic change in IOP: an initial rise in IOP of approximately 1 mm Hg from 1/2 to 1 hour followed by significant reduction in IOP of 8 to 9 mm Hg from 3 to 5 hours postadministration. These animals also exhibited a significant increase in PD of 2 to 3 mm from 1/2 to 2 hours postadministration. Pretreatment with 8-SPT (1000 microg) enhanced the initial rise in IOP, while significantly inhibiting the ocular hypotensive response. Pretreatment with 8-SPT also significantly enhanced the epinephrine-induced increase in PD. Inhibition of the epinephrine-induced reduction in IOP by 8-SPT was dose-related with an IC50 of 446 microg. Administration of 8-SPT alone did not significantly alter IOP or PD. The A2 antagonist DMPX did not alter the epinephrine-induced change in IOP or PD. In rabbits pretreated with 8-SPT, the epinephrine-induced increase in outflow facility was significantly reduced by 60% when compared with those in rabbits treated with epinephrine alone. In vehicle-treated rabbits, aqueous humor adenosine and inosine levels were 2.7 +/- 0.38 and 29 +/- 4.2 ng/100 microl, respectively. Three hours after epinephrine administration, adenosine and inosine levels had significantly increased to 11 +/- 1.6 and 66 +/- 4.4 ng/100 microl, respectively.
These results support the idea that in rabbits epinephrine administration stimulates adenosine release in the anterior segment. This rise in endogenous levels of adenosine then leads to the activation of ocular adenosine receptors and is in part responsible for the ocular hypotensive action of epinephrine.</description><subject>Adenosine - metabolism</subject><subject>Adrenergic Agonists - administration & dosage</subject><subject>Adrenergic Agonists - pharmacology</subject><subject>Animals</subject><subject>Aqueous Humor - drug effects</subject><subject>Aqueous Humor - metabolism</subject><subject>Biological and medical sciences</subject><subject>Epinephrine - administration & dosage</subject><subject>Epinephrine - pharmacology</subject><subject>Eye</subject><subject>Inosine - metabolism</subject><subject>Intraocular Pressure - drug effects</subject><subject>Medical sciences</subject><subject>Ophthalmic Solutions - administration & dosage</subject><subject>Ophthalmic Solutions - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Pupil - drug effects</subject><subject>Purinergic P1 Receptor Antagonists</subject><subject>Rabbits</subject><subject>Receptors, Purinergic P1 - metabolism</subject><subject>Theobromine - administration & dosage</subject><subject>Theobromine - analogs & derivatives</subject><subject>Theobromine - pharmacology</subject><subject>Theophylline - administration & dosage</subject><subject>Theophylline - analogs & derivatives</subject><subject>Theophylline - pharmacology</subject><issn>0146-0404</issn><issn>1552-5783</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0EtLxDAQB_AgiruufgXpQbwV8q45Lsv6gIUFH-eQplMbaZuapBa_vZVd8TJzmN9_BuYELYkQNBfFHTtFS0y4zDHHfIEuYvzAmBJC8TlaEMw5ppIs0cvG9ym4ckzO9zHzdbauoPfR9ZA9g4Uh-ZCtbXJf5ldkyWepgWxvx9YcBsfYdpgjQxPmeonOatNGuDr2FXq7375uHvPd_uFps97lDZVFylVNQNiCScqx5cIoWQKGshAgC1aJGjCzhHMFppSCV5QaYyrAlWXY8LJQbIVuD3uH4D9HiEl3LlpoW9ODH6OWSnHKFZvh9RGOZQeVHoLrTPjWf2-Ywc0RmGhNWwfTWxf_naKM0OL_YOPem8kF0LEzbTtvJXqaJo610hQLzn4AwP90fw</recordid><startdate>19990801</startdate><enddate>19990801</enddate><creator>Crosson, Craig E</creator><creator>Petrovich, Margaret</creator><general>ARVO</general><general>Association for Research in Vision and Ophtalmology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>19990801</creationdate><title>Contributions of Adenosine Receptor Activation to the Ocular Actions of Epinephrine</title><author>Crosson, Craig E ; Petrovich, Margaret</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h267t-9f1e5c736240c45a96be0eb75e673d5fe03c1449eab654d22aaade0dc30a4b793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adenosine - metabolism</topic><topic>Adrenergic Agonists - administration & dosage</topic><topic>Adrenergic Agonists - pharmacology</topic><topic>Animals</topic><topic>Aqueous Humor - drug effects</topic><topic>Aqueous Humor - metabolism</topic><topic>Biological and medical sciences</topic><topic>Epinephrine - administration & dosage</topic><topic>Epinephrine - pharmacology</topic><topic>Eye</topic><topic>Inosine - metabolism</topic><topic>Intraocular Pressure - drug effects</topic><topic>Medical sciences</topic><topic>Ophthalmic Solutions - administration & dosage</topic><topic>Ophthalmic Solutions - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Pupil - drug effects</topic><topic>Purinergic P1 Receptor Antagonists</topic><topic>Rabbits</topic><topic>Receptors, Purinergic P1 - metabolism</topic><topic>Theobromine - administration & dosage</topic><topic>Theobromine - analogs & derivatives</topic><topic>Theobromine - pharmacology</topic><topic>Theophylline - administration & dosage</topic><topic>Theophylline - analogs & derivatives</topic><topic>Theophylline - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Crosson, Craig E</creatorcontrib><creatorcontrib>Petrovich, Margaret</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Investigative ophthalmology & visual science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Crosson, Craig E</au><au>Petrovich, Margaret</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Contributions of Adenosine Receptor Activation to the Ocular Actions of Epinephrine</atitle><jtitle>Investigative ophthalmology & visual science</jtitle><addtitle>Invest Ophthalmol Vis Sci</addtitle><date>1999-08-01</date><risdate>1999</risdate><volume>40</volume><issue>9</issue><spage>2054</spage><epage>2061</epage><pages>2054-2061</pages><issn>0146-0404</issn><eissn>1552-5783</eissn><coden>IOVSDA</coden><abstract>Epinephrine is an effective drug for glaucoma treatment. However, the mechanisms responsible for the ocular hypotensive action of this compound are not completely understood. Adenosine is an autacoid released by all cells. This study evaluated the role of adenosine receptor activation in epinephrine-induced changes in ocular function.
Rabbits were pretreated topically with the moderately selective adenosine A1 antagonist 8-(p-sulfophenyl)theophylline (8-SPT) or the adenosine A2 antagonist 3,7-dimethyl-l-propargylxanthine (DMPX). Epinephrine (500 microg) was then administered, and intraocular pressures (IOPs), pupil diameters (PDs), or total outflow facility was evaluated. In a separate group of animals, epinephrine or vehicle was administered, and aqueous humor samples obtained to evaluate changes in aqueous humor purine levels by means of high-performance liquid chromatography.
In control animals, epinephrine produced a biphasic change in IOP: an initial rise in IOP of approximately 1 mm Hg from 1/2 to 1 hour followed by significant reduction in IOP of 8 to 9 mm Hg from 3 to 5 hours postadministration. These animals also exhibited a significant increase in PD of 2 to 3 mm from 1/2 to 2 hours postadministration. Pretreatment with 8-SPT (1000 microg) enhanced the initial rise in IOP, while significantly inhibiting the ocular hypotensive response. Pretreatment with 8-SPT also significantly enhanced the epinephrine-induced increase in PD. Inhibition of the epinephrine-induced reduction in IOP by 8-SPT was dose-related with an IC50 of 446 microg. Administration of 8-SPT alone did not significantly alter IOP or PD. The A2 antagonist DMPX did not alter the epinephrine-induced change in IOP or PD. In rabbits pretreated with 8-SPT, the epinephrine-induced increase in outflow facility was significantly reduced by 60% when compared with those in rabbits treated with epinephrine alone. In vehicle-treated rabbits, aqueous humor adenosine and inosine levels were 2.7 +/- 0.38 and 29 +/- 4.2 ng/100 microl, respectively. Three hours after epinephrine administration, adenosine and inosine levels had significantly increased to 11 +/- 1.6 and 66 +/- 4.4 ng/100 microl, respectively.
These results support the idea that in rabbits epinephrine administration stimulates adenosine release in the anterior segment. This rise in endogenous levels of adenosine then leads to the activation of ocular adenosine receptors and is in part responsible for the ocular hypotensive action of epinephrine.</abstract><cop>Rockville, MD</cop><pub>ARVO</pub><pmid>10440261</pmid><tpages>8</tpages></addata></record> |
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| ispartof | Investigative ophthalmology & visual science, 1999-08, Vol.40 (9), p.2054-2061 |
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| subjects | Adenosine - metabolism Adrenergic Agonists - administration & dosage Adrenergic Agonists - pharmacology Animals Aqueous Humor - drug effects Aqueous Humor - metabolism Biological and medical sciences Epinephrine - administration & dosage Epinephrine - pharmacology Eye Inosine - metabolism Intraocular Pressure - drug effects Medical sciences Ophthalmic Solutions - administration & dosage Ophthalmic Solutions - pharmacology Pharmacology. Drug treatments Pupil - drug effects Purinergic P1 Receptor Antagonists Rabbits Receptors, Purinergic P1 - metabolism Theobromine - administration & dosage Theobromine - analogs & derivatives Theobromine - pharmacology Theophylline - administration & dosage Theophylline - analogs & derivatives Theophylline - pharmacology |
| title | Contributions of Adenosine Receptor Activation to the Ocular Actions of Epinephrine |
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