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Regional brain uptake of the muscarinic ligand, [ 18F]FP-TZTP, is greatly decreased in M2 receptor knockout mice but not in M1, M3 and M4 receptor knockout mice
A muscarinic receptor radioligand, 3-(3-(3-fluoropropyl)thio) -1,2,5,thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine (fP-TZTP) radiolabeled with the positron emitting radionuclide 18F ([ 18F]FP-TZTP) displayed regional brain distribution consistent with M2 receptor densities in rat brain. The p...
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| Published in: | Neuropharmacology 2003-04, Vol.44 (5), p.653-661 |
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| cites | cdi_FETCH-LOGICAL-c474t-bc96128e71874004dec7db0820b826df88222ed55f34e51849ecf2e93da3c7eb3 |
| container_end_page | 661 |
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| container_title | Neuropharmacology |
| container_volume | 44 |
| creator | Jagoda, E.M. Kiesewetter, D.O. Shimoji, K. Ravasi, L. Yamada, M. Gomeza, J. Wess, J. Eckelman, W.C. |
| description | A muscarinic receptor radioligand, 3-(3-(3-fluoropropyl)thio) -1,2,5,thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine (fP-TZTP) radiolabeled with the positron emitting radionuclide
18F ([
18F]FP-TZTP) displayed regional brain distribution consistent with M2 receptor densities in rat brain. The purpose of the present study is to further elucidate the subtype selectivity of [
18F]FP-TZTP using genetically engineered mice which lacked functional M1, M2, M3, or M4 muscarinic receptors. Using ex vivo autoradiography, the regional brain localization of [
18F]FP-TZTP in M2 knockout (M2 KO) was significantly decreased (51.3 to 61.4%; P |
| doi_str_mv | 10.1016/S0028-3908(03)00050-9 |
| format | article |
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18F ([
18F]FP-TZTP) displayed regional brain distribution consistent with M2 receptor densities in rat brain. The purpose of the present study is to further elucidate the subtype selectivity of [
18F]FP-TZTP using genetically engineered mice which lacked functional M1, M2, M3, or M4 muscarinic receptors. Using ex vivo autoradiography, the regional brain localization of [
18F]FP-TZTP in M2 knockout (M2 KO) was significantly decreased (51.3 to 61.4%; P<0.01) when compared to the wild-type (WT) mice in amygdala, brain stem, caudate putamen, cerebellum, cortex, hippocampus, hypothalamus, superior colliculus, and thalamus. In similar studies with M1KO, M3KO and M4KO compared to their WT mice, [
18F]FP-TZTP uptakes in the same brain regions were not significantly decreased at P<0.01. However, in amygdala and hippocampus small decreases of 19.5% and 22.7%, respectively, were observed for M1KO vs WT mice at P<0.05. Given the fact that large decreases in [
18F]FP-TZTP brain uptakes were seen only in M2 KO vs. WT mice, we conclude that [
18F]FP-TZTP preferentially labels M2 receptors in vivo.</description><identifier>ISSN: 0028-3908</identifier><identifier>EISSN: 1873-7064</identifier><identifier>DOI: 10.1016/S0028-3908(03)00050-9</identifier><identifier>PMID: 12668051</identifier><identifier>CODEN: NEPHBW</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Animals ; Biological and medical sciences ; Brain - metabolism ; Cerebral blood flow ; Female ; Fluorine Radioisotopes - metabolism ; KO mice ; Ligands ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muscarinic receptors ; Pyridines - metabolism ; Receptor, Muscarinic M1 ; Receptor, Muscarinic M2 ; Receptor, Muscarinic M3 ; Receptor, Muscarinic M4 ; Receptors, Muscarinic - deficiency ; Receptors, Muscarinic - genetics ; Saturability ; Thiazoles - metabolism</subject><ispartof>Neuropharmacology, 2003-04, Vol.44 (5), p.653-661</ispartof><rights>2003 Elsevier Science Ltd</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-bc96128e71874004dec7db0820b826df88222ed55f34e51849ecf2e93da3c7eb3</citedby><cites>FETCH-LOGICAL-c474t-bc96128e71874004dec7db0820b826df88222ed55f34e51849ecf2e93da3c7eb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27898,27899</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14642071$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12668051$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jagoda, E.M.</creatorcontrib><creatorcontrib>Kiesewetter, D.O.</creatorcontrib><creatorcontrib>Shimoji, K.</creatorcontrib><creatorcontrib>Ravasi, L.</creatorcontrib><creatorcontrib>Yamada, M.</creatorcontrib><creatorcontrib>Gomeza, J.</creatorcontrib><creatorcontrib>Wess, J.</creatorcontrib><creatorcontrib>Eckelman, W.C.</creatorcontrib><title>Regional brain uptake of the muscarinic ligand, [ 18F]FP-TZTP, is greatly decreased in M2 receptor knockout mice but not in M1, M3 and M4 receptor knockout mice</title><title>Neuropharmacology</title><addtitle>Neuropharmacology</addtitle><description>A muscarinic receptor radioligand, 3-(3-(3-fluoropropyl)thio) -1,2,5,thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine (fP-TZTP) radiolabeled with the positron emitting radionuclide
18F ([
18F]FP-TZTP) displayed regional brain distribution consistent with M2 receptor densities in rat brain. The purpose of the present study is to further elucidate the subtype selectivity of [
18F]FP-TZTP using genetically engineered mice which lacked functional M1, M2, M3, or M4 muscarinic receptors. Using ex vivo autoradiography, the regional brain localization of [
18F]FP-TZTP in M2 knockout (M2 KO) was significantly decreased (51.3 to 61.4%; P<0.01) when compared to the wild-type (WT) mice in amygdala, brain stem, caudate putamen, cerebellum, cortex, hippocampus, hypothalamus, superior colliculus, and thalamus. In similar studies with M1KO, M3KO and M4KO compared to their WT mice, [
18F]FP-TZTP uptakes in the same brain regions were not significantly decreased at P<0.01. However, in amygdala and hippocampus small decreases of 19.5% and 22.7%, respectively, were observed for M1KO vs WT mice at P<0.05. Given the fact that large decreases in [
18F]FP-TZTP brain uptakes were seen only in M2 KO vs. WT mice, we conclude that [
18F]FP-TZTP preferentially labels M2 receptors in vivo.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Brain - metabolism</subject><subject>Cerebral blood flow</subject><subject>Female</subject><subject>Fluorine Radioisotopes - metabolism</subject><subject>KO mice</subject><subject>Ligands</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Muscarinic receptors</subject><subject>Pyridines - metabolism</subject><subject>Receptor, Muscarinic M1</subject><subject>Receptor, Muscarinic M2</subject><subject>Receptor, Muscarinic M3</subject><subject>Receptor, Muscarinic M4</subject><subject>Receptors, Muscarinic - deficiency</subject><subject>Receptors, Muscarinic - genetics</subject><subject>Saturability</subject><subject>Thiazoles - metabolism</subject><issn>0028-3908</issn><issn>1873-7064</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNqFkU2P0zAQhi0EYsvCTwDNBQRSA_5K4pwQWlFA2ooVlAsIWY49KaZpXOwEaf8NPxX3Q-wJ7clzeOb1zDyEPGb0JaOsevWZUq4K0VD1nIoXlNKSFs0dMmOqFkVNK3mXzP4hZ-RBSj8zJBVT98kZ41WlaMlm5M8nXPswmB7aaPwA0240G4TQwfgDYTsla6IfvIXer83g5vANmFp8X1wVq6-rqzn4BOuIZuyvwaHNVUIHOWfJIaLF3RgibIZgN2EaYestQpuLIYwHiM1hKSDnwlL-h39I7nWmT_jo9J6TL4u3q4v3xeXHdx8u3lwWVtZyLFrbVIwrrPP-Mu-Zh6ldSxWnreKV65TinKMry05ILJmSDdqOYyOcEbbGVpyTZ8fcXQy_Jkyj3vpkse_NgGFKuhaszBnqVjAPwEVVVxksj6CNIaWInd5FvzXxWjOq9w71waHeC9JU6IND3eS-J6cPpnaL7qbrJC0DT0-AyXr6LprB-nTDyUpyWu-510cO891-e4w6WY-DRefzrUftgr9llL8UHLcy</recordid><startdate>20030401</startdate><enddate>20030401</enddate><creator>Jagoda, E.M.</creator><creator>Kiesewetter, D.O.</creator><creator>Shimoji, K.</creator><creator>Ravasi, L.</creator><creator>Yamada, M.</creator><creator>Gomeza, J.</creator><creator>Wess, J.</creator><creator>Eckelman, W.C.</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>IQODW</scope><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>20030401</creationdate><title>Regional brain uptake of the muscarinic ligand, [ 18F]FP-TZTP, is greatly decreased in M2 receptor knockout mice but not in M1, M3 and M4 receptor knockout mice</title><author>Jagoda, E.M. ; Kiesewetter, D.O. ; Shimoji, K. ; Ravasi, L. ; Yamada, M. ; Gomeza, J. ; Wess, J. ; Eckelman, W.C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-bc96128e71874004dec7db0820b826df88222ed55f34e51849ecf2e93da3c7eb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Brain - metabolism</topic><topic>Cerebral blood flow</topic><topic>Female</topic><topic>Fluorine Radioisotopes - metabolism</topic><topic>KO mice</topic><topic>Ligands</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Muscarinic receptors</topic><topic>Pyridines - metabolism</topic><topic>Receptor, Muscarinic M1</topic><topic>Receptor, Muscarinic M2</topic><topic>Receptor, Muscarinic M3</topic><topic>Receptor, Muscarinic M4</topic><topic>Receptors, Muscarinic - deficiency</topic><topic>Receptors, Muscarinic - genetics</topic><topic>Saturability</topic><topic>Thiazoles - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jagoda, E.M.</creatorcontrib><creatorcontrib>Kiesewetter, D.O.</creatorcontrib><creatorcontrib>Shimoji, K.</creatorcontrib><creatorcontrib>Ravasi, L.</creatorcontrib><creatorcontrib>Yamada, M.</creatorcontrib><creatorcontrib>Gomeza, J.</creatorcontrib><creatorcontrib>Wess, J.</creatorcontrib><creatorcontrib>Eckelman, W.C.</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>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Neuropharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jagoda, E.M.</au><au>Kiesewetter, D.O.</au><au>Shimoji, K.</au><au>Ravasi, L.</au><au>Yamada, M.</au><au>Gomeza, J.</au><au>Wess, J.</au><au>Eckelman, W.C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regional brain uptake of the muscarinic ligand, [ 18F]FP-TZTP, is greatly decreased in M2 receptor knockout mice but not in M1, M3 and M4 receptor knockout mice</atitle><jtitle>Neuropharmacology</jtitle><addtitle>Neuropharmacology</addtitle><date>2003-04-01</date><risdate>2003</risdate><volume>44</volume><issue>5</issue><spage>653</spage><epage>661</epage><pages>653-661</pages><issn>0028-3908</issn><eissn>1873-7064</eissn><coden>NEPHBW</coden><abstract>A muscarinic receptor radioligand, 3-(3-(3-fluoropropyl)thio) -1,2,5,thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine (fP-TZTP) radiolabeled with the positron emitting radionuclide
18F ([
18F]FP-TZTP) displayed regional brain distribution consistent with M2 receptor densities in rat brain. The purpose of the present study is to further elucidate the subtype selectivity of [
18F]FP-TZTP using genetically engineered mice which lacked functional M1, M2, M3, or M4 muscarinic receptors. Using ex vivo autoradiography, the regional brain localization of [
18F]FP-TZTP in M2 knockout (M2 KO) was significantly decreased (51.3 to 61.4%; P<0.01) when compared to the wild-type (WT) mice in amygdala, brain stem, caudate putamen, cerebellum, cortex, hippocampus, hypothalamus, superior colliculus, and thalamus. In similar studies with M1KO, M3KO and M4KO compared to their WT mice, [
18F]FP-TZTP uptakes in the same brain regions were not significantly decreased at P<0.01. However, in amygdala and hippocampus small decreases of 19.5% and 22.7%, respectively, were observed for M1KO vs WT mice at P<0.05. Given the fact that large decreases in [
18F]FP-TZTP brain uptakes were seen only in M2 KO vs. WT mice, we conclude that [
18F]FP-TZTP preferentially labels M2 receptors in vivo.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>12668051</pmid><doi>10.1016/S0028-3908(03)00050-9</doi><tpages>9</tpages></addata></record> |
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| ispartof | Neuropharmacology, 2003-04, Vol.44 (5), p.653-661 |
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| source | Elsevier |
| subjects | Animals Biological and medical sciences Brain - metabolism Cerebral blood flow Female Fluorine Radioisotopes - metabolism KO mice Ligands Male Medical sciences Mice Mice, Inbred C57BL Mice, Knockout Muscarinic receptors Pyridines - metabolism Receptor, Muscarinic M1 Receptor, Muscarinic M2 Receptor, Muscarinic M3 Receptor, Muscarinic M4 Receptors, Muscarinic - deficiency Receptors, Muscarinic - genetics Saturability Thiazoles - metabolism |
| title | Regional brain uptake of the muscarinic ligand, [ 18F]FP-TZTP, is greatly decreased in M2 receptor knockout mice but not in M1, M3 and M4 receptor knockout mice |
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