Stimulation of Adenylyl Cyclase and Induction of Brain‐Derived Neurotrophic Factor and TrkB mRNA by NKH477, a Novel and Potent Forskolin Derivative
: The present study was undertaken to examine whether NKH477, a novel and potent water‐soluble forskolin derivative, stimulates adenylyl cyclase and regulates brain‐derived neurotrophic factor (BDNF) and TrkB expression in the rat brain. Administration of NKH477 at a dose of 1.0 mg/kg, but not 0.1 m...
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| Veröffentlicht in: | Journal of neurochemistry 1999-05, Vol.72 (5), p.2198-2205 |
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| container_title | Journal of neurochemistry |
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| creator | Morinobu, Shigeru Fujimaki, Koichiro Okuyama, Naoyuki Takahashi, Michihiro Duman, Ronald S. |
| description | : The present study was undertaken to examine whether NKH477, a novel and potent water‐soluble forskolin derivative, stimulates adenylyl cyclase and regulates brain‐derived neurotrophic factor (BDNF) and TrkB expression in the rat brain. Administration of NKH477 at a dose of 1.0 mg/kg, but not 0.1 mg/kg, increased levels of cyclic AMP (cAMP) in a time‐dependent manner in frontal cortex and hippocampus. Repeated administration of NKH477 (1.0 mg/kg) for 7 or 14 days also increased levels of cAMP in these two brain regions, indicating that the response does not desensitize with chronic treatment. In addition, administration of NKH477 at the 1 mg/kg dose increased the expression of BDNF and TrkB mRNA in frontal cortex and hippocampus. This effect was observed after single, as well as repeated (7 or 14 days), administration of NKH477. These results demonstrate that NKH477 administration rapidly increases cAMP levels in brain and provides evidence that stimulation of this second messenger system increases the expression of BDNF and TrkB mRNA. |
| doi_str_mv | 10.1046/j.1471-4159.1999.0722198.x |
| format | Article |
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Administration of NKH477 at a dose of 1.0 mg/kg, but not 0.1 mg/kg, increased levels of cyclic AMP (cAMP) in a time‐dependent manner in frontal cortex and hippocampus. Repeated administration of NKH477 (1.0 mg/kg) for 7 or 14 days also increased levels of cAMP in these two brain regions, indicating that the response does not desensitize with chronic treatment. In addition, administration of NKH477 at the 1 mg/kg dose increased the expression of BDNF and TrkB mRNA in frontal cortex and hippocampus. This effect was observed after single, as well as repeated (7 or 14 days), administration of NKH477. 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Administration of NKH477 at a dose of 1.0 mg/kg, but not 0.1 mg/kg, increased levels of cyclic AMP (cAMP) in a time‐dependent manner in frontal cortex and hippocampus. Repeated administration of NKH477 (1.0 mg/kg) for 7 or 14 days also increased levels of cAMP in these two brain regions, indicating that the response does not desensitize with chronic treatment. In addition, administration of NKH477 at the 1 mg/kg dose increased the expression of BDNF and TrkB mRNA in frontal cortex and hippocampus. This effect was observed after single, as well as repeated (7 or 14 days), administration of NKH477. These results demonstrate that NKH477 administration rapidly increases cAMP levels in brain and provides evidence that stimulation of this second messenger system increases the expression of BDNF and TrkB mRNA.</description><subject>Adenylyl cyclase</subject><subject>Adenylyl Cyclases - metabolism</subject><subject>Animals</subject><subject>Antidepressive Agents - pharmacology</subject><subject>Blotting, Northern</subject><subject>Brain - metabolism</subject><subject>Brain-Derived Neurotrophic Factor - genetics</subject><subject>Brain‐derived neurotrophic factor</subject><subject>Colforsin - analogs & derivatives</subject><subject>Colforsin - pharmacology</subject><subject>Cyclic AMP</subject><subject>Cyclic AMP - metabolism</subject><subject>Forskolin</subject><subject>Frontal Lobe - metabolism</subject><subject>Hippocampus - metabolism</subject><subject>In Situ Hybridization</subject><subject>Male</subject><subject>NKH477</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor Protein-Tyrosine Kinases - genetics</subject><subject>Receptor, Ciliary Neurotrophic Factor</subject><subject>Receptors, Nerve Growth Factor - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Time Factors</subject><subject>TrkB</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkc1u1DAURi0EokPhFZDFghUJ_kkcmw2aDgwtVAFBWVuO7YhMnXhqJ0Oz4xHY8II8CcnMgNghVr6Sz_f5ygeAJxilGGXs-SbFWYGTDOcixUKIFBWEYMHT2ztg8efqLlggREhCUUZOwIMYNwhhljF8H5xgRHBBEV2AH5_6ph2c6hvfQV_DpbHd6EYHV6N2KlqoOgMvOjPo38RZUE3389v3VzY0O2tgaYfg--C3XxoN10r3PuxDV-H6DLYfyyWsRli-O8-K4hlUsPQ76_bAB9_brodrH-K1d00H943TJjv7ENyrlYv20fE8BZ_Xr69W58nl-zcXq-VlojPGeZIJracJGVIRkufIasIIVzTHqKLcYGYMUQZzWilMlKh5zlmGVG6KWmBrK3oKnh56t8HfDDb2sm2its6pzvohSiYKjBij_wTn38wR5RP44gDq4GMMtpbb0LQqjBIjOduTGzkrkrMiOduTR3vydgo_Pr4yVK01f0UPuibg5QH42jg7_ke1fFuu5on-AvzfqjA</recordid><startdate>199905</startdate><enddate>199905</enddate><creator>Morinobu, Shigeru</creator><creator>Fujimaki, Koichiro</creator><creator>Okuyama, Naoyuki</creator><creator>Takahashi, Michihiro</creator><creator>Duman, Ronald S.</creator><general>Blackwell Publishing 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>7TK</scope><scope>7X8</scope></search><sort><creationdate>199905</creationdate><title>Stimulation of Adenylyl Cyclase and Induction of Brain‐Derived Neurotrophic Factor and TrkB mRNA by NKH477, a Novel and Potent Forskolin Derivative</title><author>Morinobu, Shigeru ; Fujimaki, Koichiro ; Okuyama, Naoyuki ; Takahashi, Michihiro ; Duman, Ronald S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4688-49ccc460d2b22550ec2628a3510b38d16dd2ad183ba12a9f858640a5d7f91eeb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adenylyl cyclase</topic><topic>Adenylyl Cyclases - metabolism</topic><topic>Animals</topic><topic>Antidepressive Agents - pharmacology</topic><topic>Blotting, Northern</topic><topic>Brain - metabolism</topic><topic>Brain-Derived Neurotrophic Factor - genetics</topic><topic>Brain‐derived neurotrophic factor</topic><topic>Colforsin - analogs & derivatives</topic><topic>Colforsin - pharmacology</topic><topic>Cyclic AMP</topic><topic>Cyclic AMP - metabolism</topic><topic>Forskolin</topic><topic>Frontal Lobe - metabolism</topic><topic>Hippocampus - metabolism</topic><topic>In Situ Hybridization</topic><topic>Male</topic><topic>NKH477</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptor Protein-Tyrosine Kinases - genetics</topic><topic>Receptor, Ciliary Neurotrophic Factor</topic><topic>Receptors, Nerve Growth Factor - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Time Factors</topic><topic>TrkB</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Morinobu, Shigeru</creatorcontrib><creatorcontrib>Fujimaki, Koichiro</creatorcontrib><creatorcontrib>Okuyama, Naoyuki</creatorcontrib><creatorcontrib>Takahashi, Michihiro</creatorcontrib><creatorcontrib>Duman, Ronald S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neurochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Morinobu, Shigeru</au><au>Fujimaki, Koichiro</au><au>Okuyama, Naoyuki</au><au>Takahashi, Michihiro</au><au>Duman, Ronald S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stimulation of Adenylyl Cyclase and Induction of Brain‐Derived Neurotrophic Factor and TrkB mRNA by NKH477, a Novel and Potent Forskolin Derivative</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>1999-05</date><risdate>1999</risdate><volume>72</volume><issue>5</issue><spage>2198</spage><epage>2205</epage><pages>2198-2205</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><abstract>: The present study was undertaken to examine whether NKH477, a novel and potent water‐soluble forskolin derivative, stimulates adenylyl cyclase and regulates brain‐derived neurotrophic factor (BDNF) and TrkB expression in the rat brain. Administration of NKH477 at a dose of 1.0 mg/kg, but not 0.1 mg/kg, increased levels of cyclic AMP (cAMP) in a time‐dependent manner in frontal cortex and hippocampus. Repeated administration of NKH477 (1.0 mg/kg) for 7 or 14 days also increased levels of cAMP in these two brain regions, indicating that the response does not desensitize with chronic treatment. In addition, administration of NKH477 at the 1 mg/kg dose increased the expression of BDNF and TrkB mRNA in frontal cortex and hippocampus. This effect was observed after single, as well as repeated (7 or 14 days), administration of NKH477. These results demonstrate that NKH477 administration rapidly increases cAMP levels in brain and provides evidence that stimulation of this second messenger system increases the expression of BDNF and TrkB mRNA.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>10217303</pmid><doi>10.1046/j.1471-4159.1999.0722198.x</doi><tpages>8</tpages></addata></record> |
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| source | MEDLINE; IngentaConnect Open Access Journals; Wiley Online Library Journals Frontfile Complete; Wiley Online Library Free Content; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | Adenylyl cyclase Adenylyl Cyclases - metabolism Animals Antidepressive Agents - pharmacology Blotting, Northern Brain - metabolism Brain-Derived Neurotrophic Factor - genetics Brain‐derived neurotrophic factor Colforsin - analogs & derivatives Colforsin - pharmacology Cyclic AMP Cyclic AMP - metabolism Forskolin Frontal Lobe - metabolism Hippocampus - metabolism In Situ Hybridization Male NKH477 Rats Rats, Sprague-Dawley Receptor Protein-Tyrosine Kinases - genetics Receptor, Ciliary Neurotrophic Factor Receptors, Nerve Growth Factor - genetics RNA, Messenger - metabolism Time Factors TrkB |
| title | Stimulation of Adenylyl Cyclase and Induction of Brain‐Derived Neurotrophic Factor and TrkB mRNA by NKH477, a Novel and Potent Forskolin Derivative |
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