G-protein coupled receptor 55 (GPR55) is a novel lipid sensing receptor activated by the endogenous lipid, lysophosphatidylinositol (LPI) and is reported as a putative cannabinoid receptor. However GPR55 shares limited homology with the two cloned cannabinoid receptors (CB1 and CB2) but does exhibit some cannabinoid sensitivity. Recently a family of bioactive lipids, the N-acyl amino acids, are gaining interest due to their structural similarity to endocannabinoids (naturally occurring CB1 and CB2 agonists). N-acyl amino acids have little or no affinity for either CB1 or CB2 and many have no known biological target at present.
This study used a subset of N-acyl amino acids; possessing either a serine or glycine head group attached to varying fatty acid chains; to assess these novel lipids as potential GPR55 ligands. Three cell lines were utilised, a stably transfected HEK293 cell line that overexpresses 3xHA N-terminus tagged hGPR55 (hGPR55-HEK293 cells) and control HEK293 cells. In addition, the DU145 a prostate cancer cell line which is reported to endogenously express GPR55 was investigated. N-acyl amino acid challenge activated GPR55 to promote Ca2+ mobilisation, CREB phosphorylation, actin cytoskeletal reorganisation and elongation of focal adhesions. Furthermore GPR55-mediated downstream signalling effectors were studied comparing LPI to the orphan lipid; N oleoyl-L-serine (NOSer).
This study highlights that N-acyl amino acids act as GPR55 agonist/partial agonists in hGPR55-HEK293 cells. Both LPI and NOSer exert effects in prostate cancer cells (DU145s) which are GPR55 mediated. GPR55 may exhibit ligand bias as LPI was more efficacious in Ca2+ mobilisation. However in the pCREB assay NOSer was more efficacious than LPI. A similar efficacy and potency to either LPI or NOSer was observed in the other assays in both hGPR55-HEK293 and DU145 cells. Furthermore this study is the first where a named GPCR can be assigned for responses that are mediated by NOSer.
","abstract_html":"<p>G-protein coupled receptor 55 (GPR55) is a novel lipid sensing receptor activated by the endogenous lipid, lysophosphatidylinositol (LPI) and is reported as a putative cannabinoid receptor. However GPR55 shares limited homology with the two cloned cannabinoid receptors (CB<sub>1</sub> and CB<sub>2</sub>) but does exhibit some cannabinoid sensitivity. Recently a family of bioactive lipids, the N-acyl amino acids, are gaining interest due to their structural similarity to endocannabinoids (naturally occurring CB<sub>1</sub> and CB<sub>2</sub> agonists). N-acyl amino acids have little or no affinity for either CB<sub>1</sub> or CB<sub>2</sub> and many have no known biological target at present.</p> <p>This study used a subset of N-acyl amino acids; possessing either a serine or glycine head group attached to varying fatty acid chains; to assess these novel lipids as potential GPR55 ligands. Three cell lines were utilised, a stably transfected HEK293 cell line that overexpresses 3xHA N-terminus tagged hGPR55 (hGPR55-HEK293 cells) and control HEK293 cells. In addition, the DU145 a prostate cancer cell line which is reported to endogenously express GPR55 was investigated. N-acyl amino acid challenge activated GPR55 to promote Ca<sup>2+</sup> mobilisation, CREB phosphorylation, actin cytoskeletal reorganisation and elongation of focal adhesions. Furthermore GPR55-mediated downstream signalling effectors were studied comparing LPI to the orphan lipid; N oleoyl-L-serine (NOSer).</p> <p>This study highlights that N-acyl amino acids act as GPR55 agonist/partial agonists in hGPR55-HEK293 cells. Both LPI and NOSer exert effects in prostate cancer cells (DU145s) which are GPR55 mediated. GPR55 may exhibit ligand bias as LPI was more efficacious in Ca<sup>2+</sup> mobilisation. However in the pCREB assay NOSer was more efficacious than LPI. A similar efficacy and potency to either LPI or NOSer was observed in the other assays in both hGPR55-HEK293 and DU145 cells. Furthermore this study is the first where a named GPCR can be assigned for responses that are mediated by NOSer.</p>","abstract_has_math":false,"creators":["Penman, June"],"institution":"University of Dundee","degree_name":"Doctor of Philosophy","degree_level":"Doctoral Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013","date_published":"2013","updated_at":"2026-07-24T02:07:52Z","subjects":[],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:discovery.dundee.ac.uk:studenttheses/2e07c280-3a61-4f49-a9da-1fa4ffc79fa5"],"render_values":[{"text":"oai:discovery.dundee.ac.uk:studenttheses/2e07c280-3a61-4f49-a9da-1fa4ffc79fa5","href":null,"code":true}]}]},"links":{"outbound_url":"https://discovery.dundee.ac.uk/en/studentTheses/2e07c280-3a61-4f49-a9da-1fa4ffc79fa5","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.sponsor","label":"Sponsor","values":["Caledonian Research Fund"]},{"key":"dc:creator","label":"Author","values":["Penman, June"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2013"]},{"key":"dc:date.issued","label":"Date","values":["2013"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Division of Neuroscience"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Dundee"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://discovery.dundee.ac.uk/en/studentTheses/2e07c280-3a61-4f49-a9da-1fa4ffc79fa5"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral Thesis"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights.embargodate","label":"Dc Rights Embargodate","values":["2017-06-28"]},{"key":"dc:rights.embargoreason","label":"Dc Rights Embargoreason","values":["/dk/atira/pure/core/document/studentthesisembargoreason/commercialexploitation"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:discovery.dundee.ac.uk:studenttheses/2e07c280-3a61-4f49-a9da-1fa4ffc79fa5","https://discovery.dundee.ac.uk/en/studentTheses/2e07c280-3a61-4f49-a9da-1fa4ffc79fa5"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://discovery.dundee.ac.uk/files/4775471/Penman_phd_2013.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["G-protein coupled receptor 55 (GPR55) is a novel lipid sensing receptor activated by the endogenous lipid, lysophosphatidylinositol (LPI) and is reported as a putative cannabinoid receptor. However GPR55 shares limited homology with the two cloned cannabinoid receptors (CB1 and CB2) but does exhibit some cannabinoid sensitivity. Recently a family of bioactive lipids, the N-acyl amino acids, are gaining interest due to their structural similarity to endocannabinoids (naturally occurring CB1 and CB2 agonists). N-acyl amino acids have little or no affinity for either CB1 or CB2 and many have no known biological target at present.
This study used a subset of N-acyl amino acids; possessing either a serine or glycine head group attached to varying fatty acid chains; to assess these novel lipids as potential GPR55 ligands. Three cell lines were utilised, a stably transfected HEK293 cell line that overexpresses 3xHA N-terminus tagged hGPR55 (hGPR55-HEK293 cells) and control HEK293 cells. In addition, the DU145 a prostate cancer cell line which is reported to endogenously express GPR55 was investigated. N-acyl amino acid challenge activated GPR55 to promote Ca2+ mobilisation, CREB phosphorylation, actin cytoskeletal reorganisation and elongation of focal adhesions. Furthermore GPR55-mediated downstream signalling effectors were studied comparing LPI to the orphan lipid; N oleoyl-L-serine (NOSer).
This study highlights that N-acyl amino acids act as GPR55 agonist/partial agonists in hGPR55-HEK293 cells. Both LPI and NOSer exert effects in prostate cancer cells (DU145s) which are GPR55 mediated. GPR55 may exhibit ligand bias as LPI was more efficacious in Ca2+ mobilisation. However in the pCREB assay NOSer was more efficacious than LPI. A similar efficacy and potency to either LPI or NOSer was observed in the other assays in both hGPR55-HEK293 and DU145 cells. Furthermore this study is the first where a named GPCR can be assigned for responses that are mediated by NOSer.
"]},{"key":"dc:title","label":"Title","values":["GPR55 and N-acyl Amino Acids"]}]}],"canonical_facts":{"dc:contributor.sponsor":["Caledonian Research Fund"],"dc:creator":["Penman, June"],"dc:date":["2013"],"dc:date.issued":["2013"],"dc:description.abstract":["G-protein coupled receptor 55 (GPR55) is a novel lipid sensing receptor activated by the endogenous lipid, lysophosphatidylinositol (LPI) and is reported as a putative cannabinoid receptor. However GPR55 shares limited homology with the two cloned cannabinoid receptors (CB1 and CB2) but does exhibit some cannabinoid sensitivity. Recently a family of bioactive lipids, the N-acyl amino acids, are gaining interest due to their structural similarity to endocannabinoids (naturally occurring CB1 and CB2 agonists). N-acyl amino acids have little or no affinity for either CB1 or CB2 and many have no known biological target at present.
This study used a subset of N-acyl amino acids; possessing either a serine or glycine head group attached to varying fatty acid chains; to assess these novel lipids as potential GPR55 ligands. Three cell lines were utilised, a stably transfected HEK293 cell line that overexpresses 3xHA N-terminus tagged hGPR55 (hGPR55-HEK293 cells) and control HEK293 cells. In addition, the DU145 a prostate cancer cell line which is reported to endogenously express GPR55 was investigated. N-acyl amino acid challenge activated GPR55 to promote Ca2+ mobilisation, CREB phosphorylation, actin cytoskeletal reorganisation and elongation of focal adhesions. Furthermore GPR55-mediated downstream signalling effectors were studied comparing LPI to the orphan lipid; N oleoyl-L-serine (NOSer).
This study highlights that N-acyl amino acids act as GPR55 agonist/partial agonists in hGPR55-HEK293 cells. Both LPI and NOSer exert effects in prostate cancer cells (DU145s) which are GPR55 mediated. GPR55 may exhibit ligand bias as LPI was more efficacious in Ca2+ mobilisation. However in the pCREB assay NOSer was more efficacious than LPI. A similar efficacy and potency to either LPI or NOSer was observed in the other assays in both hGPR55-HEK293 and DU145 cells. Furthermore this study is the first where a named GPCR can be assigned for responses that are mediated by NOSer.
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