Novel GPR18 Ligands in Rodent Pharmacological Tests: Effects on Mood, Pain, and Eating Disorders
The lack of selective pharmacological tools has limited the full unraveling of G protein-coupled receptor 18 (GPR18) functions. The present study was aimed at discovering the activities of three novel preferential or selective GPR18 ligands, one agonist (PSB-KK-1415) and two antagonists (PSB-CB-5 an...
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| Veröffentlicht in: | International journal of molecular sciences 2023-05, Vol.24 (10), p.9046 |
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| creator | Frankowska, Małgorzata Wydra, Karolina Suder, Agata Zaniewska, Magdalena Gawliński, Dawid Miszkiel, Joanna Furgała-Wojas, Anna Sałat, Kinga Filip, Małgorzata Müller, Christa E Kieć-Kononowicz, Katarzyna Kotańska, Magdalena |
| description | The lack of selective pharmacological tools has limited the full unraveling of G protein-coupled receptor 18 (GPR18) functions. The present study was aimed at discovering the activities of three novel preferential or selective GPR18 ligands, one agonist (PSB-KK-1415) and two antagonists (PSB-CB-5 and PSB-CB-27). We investigated these ligands in several screening tests, considering the relationship between GPR18 and the cannabinoid (CB) receptor system, and the control of endoCB signaling over emotions, food intake, pain sensation, and thermoregulation. We also assessed whether the novel compounds could modulate the subjective effects evoked by Δ
-tetrahydrocannabinol (THC). Male mice or rats were pretreated with the GPR18 ligands, and locomotor activity, depression- and anxiety-like symptoms, pain threshold, core temperature, food intake, and THC-vehicle discrimination were measured. Our screening analyses indicated that GPR18 activation partly results in effects that are similar to those of CB receptor activation, considering the impact on emotional behavior, food intake, and pain activity. Thus, the orphan GPR18 may provide a novel therapeutic target for mood, pain, and/or eating disorders, and further investigation is warranted to better discern its function. |
| doi_str_mv | 10.3390/ijms24109046 |
| format | Article |
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-tetrahydrocannabinol (THC). Male mice or rats were pretreated with the GPR18 ligands, and locomotor activity, depression- and anxiety-like symptoms, pain threshold, core temperature, food intake, and THC-vehicle discrimination were measured. Our screening analyses indicated that GPR18 activation partly results in effects that are similar to those of CB receptor activation, considering the impact on emotional behavior, food intake, and pain activity. Thus, the orphan GPR18 may provide a novel therapeutic target for mood, pain, and/or eating disorders, and further investigation is warranted to better discern its function.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms24109046</identifier><identifier>PMID: 37240392</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Analgesics ; Analysis ; Animals ; Antagonists ; Cannabinoid receptors ; Dose-Response Relationship, Drug ; Dronabinol - pharmacology ; Drug dosages ; Drug withdrawal ; Eating disorders ; Emotional behavior ; Feeding and Eating Disorders ; Food ; Food intake ; Health aspects ; Ligands ; Locomotor activity ; Male ; Mice ; Mood ; Pain ; Pain - drug therapy ; Pain perception ; Pharmacology ; Physiological aspects ; Physiology ; Proteins ; Rats ; Receptor mechanisms ; Receptor, Cannabinoid, CB1 ; Receptors, Cannabinoid ; Receptors, G-Protein-Coupled ; Rodentia ; Sensation ; Signs and symptoms ; Sperm ; Tetrahydrocannabinol ; THC ; Therapeutic targets ; Thermoregulation</subject><ispartof>International journal of molecular sciences, 2023-05, Vol.24 (10), p.9046</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c452t-d0b0f51f56e791c46925377ac5d4c3e4c93d774ec537129504bfb3418b1cd9473</citedby><cites>FETCH-LOGICAL-c452t-d0b0f51f56e791c46925377ac5d4c3e4c93d774ec537129504bfb3418b1cd9473</cites><orcidid>0000-0002-3946-1192 ; 0000-0002-9376-0564 ; 0000-0002-0013-6624 ; 0000-0001-9716-6661 ; 0000-0003-0614-5393 ; 0000-0002-6646-6140 ; 0000-0002-4321-7942</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10219190/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10219190/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37240392$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Frankowska, Małgorzata</creatorcontrib><creatorcontrib>Wydra, Karolina</creatorcontrib><creatorcontrib>Suder, Agata</creatorcontrib><creatorcontrib>Zaniewska, Magdalena</creatorcontrib><creatorcontrib>Gawliński, Dawid</creatorcontrib><creatorcontrib>Miszkiel, Joanna</creatorcontrib><creatorcontrib>Furgała-Wojas, Anna</creatorcontrib><creatorcontrib>Sałat, Kinga</creatorcontrib><creatorcontrib>Filip, Małgorzata</creatorcontrib><creatorcontrib>Müller, Christa E</creatorcontrib><creatorcontrib>Kieć-Kononowicz, Katarzyna</creatorcontrib><creatorcontrib>Kotańska, Magdalena</creatorcontrib><title>Novel GPR18 Ligands in Rodent Pharmacological Tests: Effects on Mood, Pain, and Eating Disorders</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>The lack of selective pharmacological tools has limited the full unraveling of G protein-coupled receptor 18 (GPR18) functions. The present study was aimed at discovering the activities of three novel preferential or selective GPR18 ligands, one agonist (PSB-KK-1415) and two antagonists (PSB-CB-5 and PSB-CB-27). We investigated these ligands in several screening tests, considering the relationship between GPR18 and the cannabinoid (CB) receptor system, and the control of endoCB signaling over emotions, food intake, pain sensation, and thermoregulation. We also assessed whether the novel compounds could modulate the subjective effects evoked by Δ
-tetrahydrocannabinol (THC). Male mice or rats were pretreated with the GPR18 ligands, and locomotor activity, depression- and anxiety-like symptoms, pain threshold, core temperature, food intake, and THC-vehicle discrimination were measured. Our screening analyses indicated that GPR18 activation partly results in effects that are similar to those of CB receptor activation, considering the impact on emotional behavior, food intake, and pain activity. Thus, the orphan GPR18 may provide a novel therapeutic target for mood, pain, and/or eating disorders, and further investigation is warranted to better discern its function.</description><subject>Analgesics</subject><subject>Analysis</subject><subject>Animals</subject><subject>Antagonists</subject><subject>Cannabinoid receptors</subject><subject>Dose-Response Relationship, Drug</subject><subject>Dronabinol - pharmacology</subject><subject>Drug dosages</subject><subject>Drug withdrawal</subject><subject>Eating disorders</subject><subject>Emotional behavior</subject><subject>Feeding and Eating Disorders</subject><subject>Food</subject><subject>Food intake</subject><subject>Health aspects</subject><subject>Ligands</subject><subject>Locomotor activity</subject><subject>Male</subject><subject>Mice</subject><subject>Mood</subject><subject>Pain</subject><subject>Pain - drug therapy</subject><subject>Pain perception</subject><subject>Pharmacology</subject><subject>Physiological aspects</subject><subject>Physiology</subject><subject>Proteins</subject><subject>Rats</subject><subject>Receptor mechanisms</subject><subject>Receptor, Cannabinoid, CB1</subject><subject>Receptors, Cannabinoid</subject><subject>Receptors, G-Protein-Coupled</subject><subject>Rodentia</subject><subject>Sensation</subject><subject>Signs and symptoms</subject><subject>Sperm</subject><subject>Tetrahydrocannabinol</subject><subject>THC</subject><subject>Therapeutic targets</subject><subject>Thermoregulation</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkUtPGzEUha2qqFBg13VlqRsWCfg5jrtBiKaAFCBCdO16_BgczdhgT5D672sUilLkha3r7557jw4AXzA6plSik7AaCmEYScSaD2APM0KmCDXi49Z7F3wuZYUQoYTLT2CXCsIQlWQP_L5Jz66HF8s7PIOL0OloCwwR3iXr4giXDzoP2qQ-dcHoHt67MpbvcO69M2OBKcLrlOwELnWIE1ib4VyPIXbwRygpW5fLAdjxui_u8PXeB79-zu_PL6eL24ur87PF1DBOxqlFLfIce944IbFhjSScCqENt8xQx4ykVgjmTK1iIjlirW8pw7MWGyuZoPvgdKP7uG4HZ03dPutePeYw6PxHJR3U_z8xPKguPSuMCJZYoqpw9KqQ09O6GlVDKMb1vY4urYsiM4IQZlLwin57h67SOsfqr1JYMi5I8yJ4vKE63TsVok91sKnHuiGYFJ0PtX4mOGGEyWZWGyabBpNTKdn5t_UxUi9hq-2wK_512_Ib_C9d-heUYKMa</recordid><startdate>20230520</startdate><enddate>20230520</enddate><creator>Frankowska, Małgorzata</creator><creator>Wydra, Karolina</creator><creator>Suder, Agata</creator><creator>Zaniewska, Magdalena</creator><creator>Gawliński, Dawid</creator><creator>Miszkiel, Joanna</creator><creator>Furgała-Wojas, Anna</creator><creator>Sałat, Kinga</creator><creator>Filip, Małgorzata</creator><creator>Müller, Christa E</creator><creator>Kieć-Kononowicz, Katarzyna</creator><creator>Kotańska, Magdalena</creator><general>MDPI AG</general><general>MDPI</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3946-1192</orcidid><orcidid>https://orcid.org/0000-0002-9376-0564</orcidid><orcidid>https://orcid.org/0000-0002-0013-6624</orcidid><orcidid>https://orcid.org/0000-0001-9716-6661</orcidid><orcidid>https://orcid.org/0000-0003-0614-5393</orcidid><orcidid>https://orcid.org/0000-0002-6646-6140</orcidid><orcidid>https://orcid.org/0000-0002-4321-7942</orcidid></search><sort><creationdate>20230520</creationdate><title>Novel GPR18 Ligands in Rodent Pharmacological Tests: Effects on Mood, Pain, and Eating Disorders</title><author>Frankowska, Małgorzata ; Wydra, Karolina ; Suder, Agata ; Zaniewska, Magdalena ; Gawliński, Dawid ; Miszkiel, Joanna ; Furgała-Wojas, Anna ; Sałat, Kinga ; Filip, Małgorzata ; Müller, Christa E ; Kieć-Kononowicz, Katarzyna ; Kotańska, Magdalena</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c452t-d0b0f51f56e791c46925377ac5d4c3e4c93d774ec537129504bfb3418b1cd9473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Analgesics</topic><topic>Analysis</topic><topic>Animals</topic><topic>Antagonists</topic><topic>Cannabinoid receptors</topic><topic>Dose-Response Relationship, Drug</topic><topic>Dronabinol - 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The present study was aimed at discovering the activities of three novel preferential or selective GPR18 ligands, one agonist (PSB-KK-1415) and two antagonists (PSB-CB-5 and PSB-CB-27). We investigated these ligands in several screening tests, considering the relationship between GPR18 and the cannabinoid (CB) receptor system, and the control of endoCB signaling over emotions, food intake, pain sensation, and thermoregulation. We also assessed whether the novel compounds could modulate the subjective effects evoked by Δ
-tetrahydrocannabinol (THC). Male mice or rats were pretreated with the GPR18 ligands, and locomotor activity, depression- and anxiety-like symptoms, pain threshold, core temperature, food intake, and THC-vehicle discrimination were measured. Our screening analyses indicated that GPR18 activation partly results in effects that are similar to those of CB receptor activation, considering the impact on emotional behavior, food intake, and pain activity. Thus, the orphan GPR18 may provide a novel therapeutic target for mood, pain, and/or eating disorders, and further investigation is warranted to better discern its function.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>37240392</pmid><doi>10.3390/ijms24109046</doi><orcidid>https://orcid.org/0000-0002-3946-1192</orcidid><orcidid>https://orcid.org/0000-0002-9376-0564</orcidid><orcidid>https://orcid.org/0000-0002-0013-6624</orcidid><orcidid>https://orcid.org/0000-0001-9716-6661</orcidid><orcidid>https://orcid.org/0000-0003-0614-5393</orcidid><orcidid>https://orcid.org/0000-0002-6646-6140</orcidid><orcidid>https://orcid.org/0000-0002-4321-7942</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | International journal of molecular sciences, 2023-05, Vol.24 (10), p.9046 |
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| language | eng |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Analgesics Analysis Animals Antagonists Cannabinoid receptors Dose-Response Relationship, Drug Dronabinol - pharmacology Drug dosages Drug withdrawal Eating disorders Emotional behavior Feeding and Eating Disorders Food Food intake Health aspects Ligands Locomotor activity Male Mice Mood Pain Pain - drug therapy Pain perception Pharmacology Physiological aspects Physiology Proteins Rats Receptor mechanisms Receptor, Cannabinoid, CB1 Receptors, Cannabinoid Receptors, G-Protein-Coupled Rodentia Sensation Signs and symptoms Sperm Tetrahydrocannabinol THC Therapeutic targets Thermoregulation |
| title | Novel GPR18 Ligands in Rodent Pharmacological Tests: Effects on Mood, Pain, and Eating Disorders |
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