Nitroglycerin increases serotonin transporter expression in rat spinal cord but anandamide modulated this effect
•Administration of NTG and AEA alone are able to increase the expression of 5-HTT at the level of TNC.•The combined nitroglycerin and anandamide treatment attenuated this effect.•A complex interaction might be present between the serotoninergic, nitrergic and the endocannabinoid system. Migraine is...
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| Veröffentlicht in: | Journal of chemical neuroanatomy 2017-11, Vol.85, p.13-20 |
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| creator | Nagy-Grócz, Gábor Bohár, Zsuzsanna Fejes-Szabó, Annamária Laborc, Klaudia Flóra Spekker, Eleonóra Tar, Lilla Vécsei, László Párdutz, Árpád |
| description | •Administration of NTG and AEA alone are able to increase the expression of 5-HTT at the level of TNC.•The combined nitroglycerin and anandamide treatment attenuated this effect.•A complex interaction might be present between the serotoninergic, nitrergic and the endocannabinoid system.
Migraine is one of the most prevalent neurological diseases, which affects 16% of the total population. The exact pathomechanism of this disorder is still not well understood, but it seems that serotonin and its transporter have a crucial role in the pathogenesis.
One of the animal models of migraine is the systemic administration of nitroglycerin (NTG), a nitric oxide (NO) donor. NO can initiate a central sensitization process in the trigeminal system, which is also present in migraineurs.
Recent studies showed that the endocannabinoid system has a modulatory role on the trigeminal activation and sensitization.
Our aim was to investigate the effect of an endogenous cannabinoid, anandamide (AEA) on the NTG-induced changes on serotonin transporter (5-HTT) expression in the upper cervical spinal cord (C1–C2) of the rat, where most of the trigeminal nociceptive afferents convey.
The animals were divided into four groups. Rats in the first group, called placebo, received only the vehicle solution as treatment. In the second group, they were treated with an intraperitoneal (i.p.) injection of NTG (10mg/kg). Rats in the third and fourth groups received i.p. AEA (2×5mg/kg) half hour before and one hour after the placebo or NTG treatment. Four hours after placebo/NTG injection, the animals were perfused and the cervical spinal cords were removed for immunohistochemistry and Western blotting.
Our results show that both NTG and AEA alone are able to increase 5-HTT expression in the C1–C2 segments. Combination of NTG and AEA has an opposing effect on this marker, nullifying the effects of non-combined administration, probably by negative feedback mechanisms. |
| doi_str_mv | 10.1016/j.jchemneu.2017.06.002 |
| format | Article |
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Migraine is one of the most prevalent neurological diseases, which affects 16% of the total population. The exact pathomechanism of this disorder is still not well understood, but it seems that serotonin and its transporter have a crucial role in the pathogenesis.
One of the animal models of migraine is the systemic administration of nitroglycerin (NTG), a nitric oxide (NO) donor. NO can initiate a central sensitization process in the trigeminal system, which is also present in migraineurs.
Recent studies showed that the endocannabinoid system has a modulatory role on the trigeminal activation and sensitization.
Our aim was to investigate the effect of an endogenous cannabinoid, anandamide (AEA) on the NTG-induced changes on serotonin transporter (5-HTT) expression in the upper cervical spinal cord (C1–C2) of the rat, where most of the trigeminal nociceptive afferents convey.
The animals were divided into four groups. Rats in the first group, called placebo, received only the vehicle solution as treatment. In the second group, they were treated with an intraperitoneal (i.p.) injection of NTG (10mg/kg). Rats in the third and fourth groups received i.p. AEA (2×5mg/kg) half hour before and one hour after the placebo or NTG treatment. Four hours after placebo/NTG injection, the animals were perfused and the cervical spinal cords were removed for immunohistochemistry and Western blotting.
Our results show that both NTG and AEA alone are able to increase 5-HTT expression in the C1–C2 segments. Combination of NTG and AEA has an opposing effect on this marker, nullifying the effects of non-combined administration, probably by negative feedback mechanisms.</description><identifier>ISSN: 0891-0618</identifier><identifier>EISSN: 1873-6300</identifier><identifier>DOI: 10.1016/j.jchemneu.2017.06.002</identifier><identifier>PMID: 28625856</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Anandamide ; Animals ; Arachidonic Acids - pharmacology ; Cannabinoid Receptor Agonists - pharmacology ; Endocannabinoids - pharmacology ; Male ; Migraine ; Nitric Oxide Donors - pharmacology ; Nitroglycerin ; Nitroglycerin - pharmacology ; Polyunsaturated Alkamides - pharmacology ; Rats ; Rats, Sprague-Dawley ; Serotonin ; Serotonin Plasma Membrane Transport Proteins - metabolism ; Serotonin transporter ; Spinal Cord - drug effects ; Spinal Cord - metabolism ; Trigeminal system</subject><ispartof>Journal of chemical neuroanatomy, 2017-11, Vol.85, p.13-20</ispartof><rights>2017 Elsevier B.V.</rights><rights>Copyright © 2017 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c368t-7a5232c3b27c05c1d76754c1b976b47906521e227af0f83881ac6b8551dfaf8e3</citedby><cites>FETCH-LOGICAL-c368t-7a5232c3b27c05c1d76754c1b976b47906521e227af0f83881ac6b8551dfaf8e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jchemneu.2017.06.002$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28625856$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nagy-Grócz, Gábor</creatorcontrib><creatorcontrib>Bohár, Zsuzsanna</creatorcontrib><creatorcontrib>Fejes-Szabó, Annamária</creatorcontrib><creatorcontrib>Laborc, Klaudia Flóra</creatorcontrib><creatorcontrib>Spekker, Eleonóra</creatorcontrib><creatorcontrib>Tar, Lilla</creatorcontrib><creatorcontrib>Vécsei, László</creatorcontrib><creatorcontrib>Párdutz, Árpád</creatorcontrib><title>Nitroglycerin increases serotonin transporter expression in rat spinal cord but anandamide modulated this effect</title><title>Journal of chemical neuroanatomy</title><addtitle>J Chem Neuroanat</addtitle><description>•Administration of NTG and AEA alone are able to increase the expression of 5-HTT at the level of TNC.•The combined nitroglycerin and anandamide treatment attenuated this effect.•A complex interaction might be present between the serotoninergic, nitrergic and the endocannabinoid system.
Migraine is one of the most prevalent neurological diseases, which affects 16% of the total population. The exact pathomechanism of this disorder is still not well understood, but it seems that serotonin and its transporter have a crucial role in the pathogenesis.
One of the animal models of migraine is the systemic administration of nitroglycerin (NTG), a nitric oxide (NO) donor. NO can initiate a central sensitization process in the trigeminal system, which is also present in migraineurs.
Recent studies showed that the endocannabinoid system has a modulatory role on the trigeminal activation and sensitization.
Our aim was to investigate the effect of an endogenous cannabinoid, anandamide (AEA) on the NTG-induced changes on serotonin transporter (5-HTT) expression in the upper cervical spinal cord (C1–C2) of the rat, where most of the trigeminal nociceptive afferents convey.
The animals were divided into four groups. Rats in the first group, called placebo, received only the vehicle solution as treatment. In the second group, they were treated with an intraperitoneal (i.p.) injection of NTG (10mg/kg). Rats in the third and fourth groups received i.p. AEA (2×5mg/kg) half hour before and one hour after the placebo or NTG treatment. Four hours after placebo/NTG injection, the animals were perfused and the cervical spinal cords were removed for immunohistochemistry and Western blotting.
Our results show that both NTG and AEA alone are able to increase 5-HTT expression in the C1–C2 segments. Combination of NTG and AEA has an opposing effect on this marker, nullifying the effects of non-combined administration, probably by negative feedback mechanisms.</description><subject>Anandamide</subject><subject>Animals</subject><subject>Arachidonic Acids - pharmacology</subject><subject>Cannabinoid Receptor Agonists - pharmacology</subject><subject>Endocannabinoids - pharmacology</subject><subject>Male</subject><subject>Migraine</subject><subject>Nitric Oxide Donors - pharmacology</subject><subject>Nitroglycerin</subject><subject>Nitroglycerin - pharmacology</subject><subject>Polyunsaturated Alkamides - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Serotonin</subject><subject>Serotonin Plasma Membrane Transport Proteins - metabolism</subject><subject>Serotonin transporter</subject><subject>Spinal Cord - drug effects</subject><subject>Spinal Cord - metabolism</subject><subject>Trigeminal system</subject><issn>0891-0618</issn><issn>1873-6300</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1v1DAQhi0EotuPv1D5yCXBY68d5waqKCBVcKFny7En1KvEDraD6L9vVtty7Wmk0fPOq3kIuQbWAgP18dAe3APOEdeWM-haplrG-BuyA92JRgnG3pId0z00TIE-I-elHBgDKfbqPTnjWnGppdqR5UeoOf2eHh3mEGmILqMtWGjBnGqK265mG8uScsVM8d-SsZSQjijNttKyhGgn6lL2dFgrtdFGb-fgkc7Jr5Ot6Gl9CIXiOKKrl-TdaKeCV8_zgtzffvl18625-_n1-83nu8YJpWvTWckFd2LgnWPSge9UJ_cOhr5Tw77rmZIckPPOjmzUQmuwTg1aSvCjHTWKC_LhdHfJ6c-KpZo5FIfTZCOmtRjoAaDvlRAbqk6oy6mUjKNZcphtfjTAzNG2OZgX2-Zo2zBlNttb8Pq5Yx1m9P9jL3o34NMJwO3TvwGzKS5gdOhD3lwYn8JrHU9ZnpaK</recordid><startdate>201711</startdate><enddate>201711</enddate><creator>Nagy-Grócz, Gábor</creator><creator>Bohár, Zsuzsanna</creator><creator>Fejes-Szabó, Annamária</creator><creator>Laborc, Klaudia Flóra</creator><creator>Spekker, Eleonóra</creator><creator>Tar, Lilla</creator><creator>Vécsei, László</creator><creator>Párdutz, Árpád</creator><general>Elsevier B.V</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>201711</creationdate><title>Nitroglycerin increases serotonin transporter expression in rat spinal cord but anandamide modulated this effect</title><author>Nagy-Grócz, Gábor ; Bohár, Zsuzsanna ; Fejes-Szabó, Annamária ; Laborc, Klaudia Flóra ; Spekker, Eleonóra ; Tar, Lilla ; Vécsei, László ; Párdutz, Árpád</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c368t-7a5232c3b27c05c1d76754c1b976b47906521e227af0f83881ac6b8551dfaf8e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Anandamide</topic><topic>Animals</topic><topic>Arachidonic Acids - pharmacology</topic><topic>Cannabinoid Receptor Agonists - pharmacology</topic><topic>Endocannabinoids - pharmacology</topic><topic>Male</topic><topic>Migraine</topic><topic>Nitric Oxide Donors - pharmacology</topic><topic>Nitroglycerin</topic><topic>Nitroglycerin - pharmacology</topic><topic>Polyunsaturated Alkamides - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Serotonin</topic><topic>Serotonin Plasma Membrane Transport Proteins - metabolism</topic><topic>Serotonin transporter</topic><topic>Spinal Cord - drug effects</topic><topic>Spinal Cord - metabolism</topic><topic>Trigeminal system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nagy-Grócz, Gábor</creatorcontrib><creatorcontrib>Bohár, Zsuzsanna</creatorcontrib><creatorcontrib>Fejes-Szabó, Annamária</creatorcontrib><creatorcontrib>Laborc, Klaudia Flóra</creatorcontrib><creatorcontrib>Spekker, Eleonóra</creatorcontrib><creatorcontrib>Tar, Lilla</creatorcontrib><creatorcontrib>Vécsei, László</creatorcontrib><creatorcontrib>Párdutz, Árpád</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>Journal of chemical neuroanatomy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nagy-Grócz, Gábor</au><au>Bohár, Zsuzsanna</au><au>Fejes-Szabó, Annamária</au><au>Laborc, Klaudia Flóra</au><au>Spekker, Eleonóra</au><au>Tar, Lilla</au><au>Vécsei, László</au><au>Párdutz, Árpád</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nitroglycerin increases serotonin transporter expression in rat spinal cord but anandamide modulated this effect</atitle><jtitle>Journal of chemical neuroanatomy</jtitle><addtitle>J Chem Neuroanat</addtitle><date>2017-11</date><risdate>2017</risdate><volume>85</volume><spage>13</spage><epage>20</epage><pages>13-20</pages><issn>0891-0618</issn><eissn>1873-6300</eissn><abstract>•Administration of NTG and AEA alone are able to increase the expression of 5-HTT at the level of TNC.•The combined nitroglycerin and anandamide treatment attenuated this effect.•A complex interaction might be present between the serotoninergic, nitrergic and the endocannabinoid system.
Migraine is one of the most prevalent neurological diseases, which affects 16% of the total population. The exact pathomechanism of this disorder is still not well understood, but it seems that serotonin and its transporter have a crucial role in the pathogenesis.
One of the animal models of migraine is the systemic administration of nitroglycerin (NTG), a nitric oxide (NO) donor. NO can initiate a central sensitization process in the trigeminal system, which is also present in migraineurs.
Recent studies showed that the endocannabinoid system has a modulatory role on the trigeminal activation and sensitization.
Our aim was to investigate the effect of an endogenous cannabinoid, anandamide (AEA) on the NTG-induced changes on serotonin transporter (5-HTT) expression in the upper cervical spinal cord (C1–C2) of the rat, where most of the trigeminal nociceptive afferents convey.
The animals were divided into four groups. Rats in the first group, called placebo, received only the vehicle solution as treatment. In the second group, they were treated with an intraperitoneal (i.p.) injection of NTG (10mg/kg). Rats in the third and fourth groups received i.p. AEA (2×5mg/kg) half hour before and one hour after the placebo or NTG treatment. Four hours after placebo/NTG injection, the animals were perfused and the cervical spinal cords were removed for immunohistochemistry and Western blotting.
Our results show that both NTG and AEA alone are able to increase 5-HTT expression in the C1–C2 segments. Combination of NTG and AEA has an opposing effect on this marker, nullifying the effects of non-combined administration, probably by negative feedback mechanisms.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>28625856</pmid><doi>10.1016/j.jchemneu.2017.06.002</doi><tpages>8</tpages></addata></record> |
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| subjects | Anandamide Animals Arachidonic Acids - pharmacology Cannabinoid Receptor Agonists - pharmacology Endocannabinoids - pharmacology Male Migraine Nitric Oxide Donors - pharmacology Nitroglycerin Nitroglycerin - pharmacology Polyunsaturated Alkamides - pharmacology Rats Rats, Sprague-Dawley Serotonin Serotonin Plasma Membrane Transport Proteins - metabolism Serotonin transporter Spinal Cord - drug effects Spinal Cord - metabolism Trigeminal system |
| title | Nitroglycerin increases serotonin transporter expression in rat spinal cord but anandamide modulated this effect |
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