Displacement of Serotonin from Its Adenosine Triphosphate Complex by Tricyclic Antidepressant Drugs in Vitro
Serotonin forms a high molecular weight micellar complex with ATP, which is assumed to be the storage form of the neurotransmitter in nerve ending granules. Since bound serotonin (5-HT) does not show fluorescence, complex formation is accompanied by quenching of its fluorescence. Using a solution of...
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| Veröffentlicht in: | Molecular pharmacology 1975-11, Vol.11 (6), p.795-802 |
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| container_title | Molecular pharmacology |
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| creator | Nogrady, T Nogrady, H I Hrdina, P D Ling, G M |
| description | Serotonin forms a high molecular weight micellar complex with ATP, which is assumed
to be the storage form of the neurotransmitter in nerve ending granules. Since bound
serotonin (5-HT) does not show fluorescence, complex formation is accompanied by
quenching of its fluorescence. Using a solution of a 5-HT-ATP complex at a 1:2 molar
ratio containing 5 mM 5-HT, we observed fluorescence enhancement upon addition of
tricyclic antidepressants in proportion to the amount and nature of the drug. The molar
ratio of drug to 5-HT necessary to liberate 50% of bound serotonin was used to characterize the relative efficacy of the drugs
in competing with 5-HT for ATP. The drugs also
form water-insoluble complexes with ATP in a 2:1 molar ratio even in the presence of 5-HT. The solid complexes were characterized
by infrared and NMR spectroscopy as well
as by elemental analysis. The liberation of 5-HT from its "storage complex" in vitro
suggests that an intraneuronal mode of action of antidepressant drugs is possible, in
addition to their known inhibition of reuptake at the presynaptic neuronal membrane. |
| format | Article |
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to be the storage form of the neurotransmitter in nerve ending granules. Since bound
serotonin (5-HT) does not show fluorescence, complex formation is accompanied by
quenching of its fluorescence. Using a solution of a 5-HT-ATP complex at a 1:2 molar
ratio containing 5 mM 5-HT, we observed fluorescence enhancement upon addition of
tricyclic antidepressants in proportion to the amount and nature of the drug. The molar
ratio of drug to 5-HT necessary to liberate 50% of bound serotonin was used to characterize the relative efficacy of the drugs
in competing with 5-HT for ATP. The drugs also
form water-insoluble complexes with ATP in a 2:1 molar ratio even in the presence of 5-HT. The solid complexes were characterized
by infrared and NMR spectroscopy as well
as by elemental analysis. The liberation of 5-HT from its "storage complex" in vitro
suggests that an intraneuronal mode of action of antidepressant drugs is possible, in
addition to their known inhibition of reuptake at the presynaptic neuronal membrane.</description><identifier>ISSN: 0026-895X</identifier><identifier>EISSN: 1521-0111</identifier><identifier>PMID: 1207673</identifier><language>eng</language><publisher>United States: American Society for Pharmacology and Experimental Therapeutics</publisher><subject>Adenosine Triphosphate - metabolism ; Antidepressive Agents, Tricyclic - metabolism ; Antidepressive Agents, Tricyclic - pharmacology ; Binding, Competitive - drug effects ; Fluorescence ; In Vitro Techniques ; Magnesium - pharmacology ; Magnetic Resonance Spectroscopy ; Serotonin - metabolism ; Spectrometry, Fluorescence</subject><ispartof>Molecular pharmacology, 1975-11, Vol.11 (6), p.795-802</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1207673$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nogrady, T</creatorcontrib><creatorcontrib>Nogrady, H I</creatorcontrib><creatorcontrib>Hrdina, P D</creatorcontrib><creatorcontrib>Ling, G M</creatorcontrib><title>Displacement of Serotonin from Its Adenosine Triphosphate Complex by Tricyclic Antidepressant Drugs in Vitro</title><title>Molecular pharmacology</title><addtitle>Mol Pharmacol</addtitle><description>Serotonin forms a high molecular weight micellar complex with ATP, which is assumed
to be the storage form of the neurotransmitter in nerve ending granules. Since bound
serotonin (5-HT) does not show fluorescence, complex formation is accompanied by
quenching of its fluorescence. Using a solution of a 5-HT-ATP complex at a 1:2 molar
ratio containing 5 mM 5-HT, we observed fluorescence enhancement upon addition of
tricyclic antidepressants in proportion to the amount and nature of the drug. The molar
ratio of drug to 5-HT necessary to liberate 50% of bound serotonin was used to characterize the relative efficacy of the drugs
in competing with 5-HT for ATP. The drugs also
form water-insoluble complexes with ATP in a 2:1 molar ratio even in the presence of 5-HT. The solid complexes were characterized
by infrared and NMR spectroscopy as well
as by elemental analysis. The liberation of 5-HT from its "storage complex" in vitro
suggests that an intraneuronal mode of action of antidepressant drugs is possible, in
addition to their known inhibition of reuptake at the presynaptic neuronal membrane.</description><subject>Adenosine Triphosphate - metabolism</subject><subject>Antidepressive Agents, Tricyclic - metabolism</subject><subject>Antidepressive Agents, Tricyclic - pharmacology</subject><subject>Binding, Competitive - drug effects</subject><subject>Fluorescence</subject><subject>In Vitro Techniques</subject><subject>Magnesium - pharmacology</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Serotonin - metabolism</subject><subject>Spectrometry, Fluorescence</subject><issn>0026-895X</issn><issn>1521-0111</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1975</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNotkE1LAzEQhoMotVZ_gpCL3hYm2WY3eyytX1DwYBVvS5qddiPZzZpk0f57I-1p4H3eeWDmjEyZ4CwDxtg5mQLwIpOV-LwkVyF8AbC5kDAhE8ahLMp8SuzKhMEqjR32kbodfUPvoutNT3fedfQlBrposHfB9Eg33gytC0OrItKl6waLv3R7-M_1QVuj6aKPpsHBYwgqCVd-3AeaZB8mendNLnbKBrw5zRl5f3zYLJ-z9evTy3KxzlomWMxEU0mmZAUKJUJRFYoXpdZlLpjOOeegkc0rKRKClO0AGmCpvVWKo8x1PiP3R-_g3feIIdadCRqtVT26MdQy5wzKtDwjt6fiuO2wqQdvOuUP9ek9id8deWv27Y_xWKfTfae0s26faqwu6rIS-R-5Ym-s</recordid><startdate>197511</startdate><enddate>197511</enddate><creator>Nogrady, T</creator><creator>Nogrady, H I</creator><creator>Hrdina, P D</creator><creator>Ling, G M</creator><general>American Society for Pharmacology and Experimental Therapeutics</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>197511</creationdate><title>Displacement of Serotonin from Its Adenosine Triphosphate Complex by Tricyclic Antidepressant Drugs in Vitro</title><author>Nogrady, T ; Nogrady, H I ; Hrdina, P D ; Ling, G M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h151t-5d981a890ae8e0696a267cc7351c32220ce149850690351f00d0190abaa2e83c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1975</creationdate><topic>Adenosine Triphosphate - metabolism</topic><topic>Antidepressive Agents, Tricyclic - metabolism</topic><topic>Antidepressive Agents, Tricyclic - pharmacology</topic><topic>Binding, Competitive - drug effects</topic><topic>Fluorescence</topic><topic>In Vitro Techniques</topic><topic>Magnesium - pharmacology</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Serotonin - metabolism</topic><topic>Spectrometry, Fluorescence</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nogrady, T</creatorcontrib><creatorcontrib>Nogrady, H I</creatorcontrib><creatorcontrib>Hrdina, P D</creatorcontrib><creatorcontrib>Ling, G M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nogrady, T</au><au>Nogrady, H I</au><au>Hrdina, P D</au><au>Ling, G M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Displacement of Serotonin from Its Adenosine Triphosphate Complex by Tricyclic Antidepressant Drugs in Vitro</atitle><jtitle>Molecular pharmacology</jtitle><addtitle>Mol Pharmacol</addtitle><date>1975-11</date><risdate>1975</risdate><volume>11</volume><issue>6</issue><spage>795</spage><epage>802</epage><pages>795-802</pages><issn>0026-895X</issn><eissn>1521-0111</eissn><abstract>Serotonin forms a high molecular weight micellar complex with ATP, which is assumed
to be the storage form of the neurotransmitter in nerve ending granules. Since bound
serotonin (5-HT) does not show fluorescence, complex formation is accompanied by
quenching of its fluorescence. Using a solution of a 5-HT-ATP complex at a 1:2 molar
ratio containing 5 mM 5-HT, we observed fluorescence enhancement upon addition of
tricyclic antidepressants in proportion to the amount and nature of the drug. The molar
ratio of drug to 5-HT necessary to liberate 50% of bound serotonin was used to characterize the relative efficacy of the drugs
in competing with 5-HT for ATP. The drugs also
form water-insoluble complexes with ATP in a 2:1 molar ratio even in the presence of 5-HT. The solid complexes were characterized
by infrared and NMR spectroscopy as well
as by elemental analysis. The liberation of 5-HT from its "storage complex" in vitro
suggests that an intraneuronal mode of action of antidepressant drugs is possible, in
addition to their known inhibition of reuptake at the presynaptic neuronal membrane.</abstract><cop>United States</cop><pub>American Society for Pharmacology and Experimental Therapeutics</pub><pmid>1207673</pmid><tpages>8</tpages></addata></record> |
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| ispartof | Molecular pharmacology, 1975-11, Vol.11 (6), p.795-802 |
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| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Adenosine Triphosphate - metabolism Antidepressive Agents, Tricyclic - metabolism Antidepressive Agents, Tricyclic - pharmacology Binding, Competitive - drug effects Fluorescence In Vitro Techniques Magnesium - pharmacology Magnetic Resonance Spectroscopy Serotonin - metabolism Spectrometry, Fluorescence |
| title | Displacement of Serotonin from Its Adenosine Triphosphate Complex by Tricyclic Antidepressant Drugs in Vitro |
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