title: Evaluation of cannabinoid receptor 2 and metabotropic glutamate receptor 1 functional responses using a cell impedance-based technology.
abstract: Recently, new technologies based on biosensors and called label free have been developed. These technologies eliminate the need for using markers and dyes. The authors applied one of these technologies, based on measurement of cell impedance variation, to study the pharmacological profiles of ligands for the cannabinoid receptor 2 (CB2), a Gi-coupled receptor, and for the metabopotropic glutamate receptor 1 (mGluR1), a Gq-coupled receptor. Reference agonists and antagonists/inverse agonists for the 2 receptors were applied to recombinant cell lines and impedance monitored over time. Agonists (JWH133 and CP55940 for CB2; quisqualate, glutamate, 1S-3R-ACPD, and S-3,5-DHPG for mGluR1) triggered a variation of impedance consistent in both potency and efficacy with data obtained using classical assays measuring cAMP or Ca(2+) levels. This effect was not present in the parental nontransfected cell line, confirming specific receptor-mediated response. Application of antagonists (AM630 for CB2; YM298198, SCH1014222, J&J16259685, and CPCCOEt for mGluR1) reduced agonist-induced impedance changes. The only exception was the mGluR1 antagonist BAY367620 that, while active in the Ca(2+) assay, was inactive in the impedance assay. Overall, these results confirm the possibility of using cell impedance-based technology to study the pharmacological profile of ligands acting at G-protein-coupled receptors coupled to different downstream signaling pathways.
authors.affiliation: Schering-Plough Research Institute, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Scandroglio
authors.forename: Rossella
authors.initials: R
authors.lastname: Brusa
authors.forename: Gianluca
authors.initials: G
authors.lastname: Lozza
authors.forename: Isabella
authors.initials: I
authors.lastname: Mancini
authors.forename: Roberta
authors.initials: R
authors.lastname: Petrò
authors.forename: Angelo
authors.initials: A
authors.lastname: Reggiani
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Beltramo
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001681:Biological Assay; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002186:Cannabinoids / Q000494:pharmacology; D002867:Chromones; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D003511:Cyclohexanols / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D017097:Electric Impedance; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012118:Resorcinols / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: C495417:(3,4-dihydro-2H-pyrano(2,3)b-quinolin-7-yl)-(cis-4-methoxycyclohexyl) methanone; C505455:6-amino-N-cyclohexyl-N,3-dimethylthiazolo(3,2-a)benzimidazole-2-carboxamide; C117789:7-(hydroxyimino)cyclopropan(b)chromen-1a-carbxoylic acid ethyl ester; D000700:Analgesics; C425484:BAY36-7620; D001562:Benzimidazoles; D002186:Cannabinoids; D002867:Chromones; D003511:Cyclohexanols; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007211:Indoles; D009281:Naphthalenes; D018696:Neuroprotective Agents; D011804:Quinolines; D043885:Receptor, Cannabinoid, CB2; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; D013844:Thiazoles; C104077:metabotropic glutamate receptor type 1; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D018698:Glutamic Acid; C079215:3,5-dihydroxyphenylglycine; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D016318:Quisqualic Acid; D000242:Cyclic AMP; D002118:Calcium; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC; D005998:Glycine; C094023:iodopravadoline