title: Interaction of D₃ preferring agonist (-)-N⁶-(2-(4-(biphenyl-4-yl)piperazin-1-yl)ethyl)-N⁶-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine (D-264) with cloned human D₂L, D₂S, and D₃ receptors: potent stimulation of mitogen-activated protein kinases and G protein-coupled inward rectifier potassium channels.
abstract: This study aims to determine the effect of the novel D(3) dopamine receptor agonist, D-264, on activation of D(3) and D(2) dopamine receptor signal transduction pathways and cell proliferation. AtT-20 neuroendocrine cells stably expressing human D(2S), D(2L), and D(3) dopamine receptors were treated with D-264 and the coupling of the receptors to mitogen-activated protein kinase (MAPK) and G protein-coupled inward rectifier potassium (GIRK) channels was determined using Western blotting and whole-cell voltage clamp recording, respectively. D-264 potently activated MAPK signaling pathway coupled to D(2S), D(2L), and D(3) dopamine receptors. The activation of MAPK was more pronounced than the reference agonist quinpirole and was longer lasting. D-264 also activated GIRK channels coupled to D(2S), D(2L), and D(3) receptors. In addition, D-264 dose-dependently induced cell proliferation in AtT-D(2L) and AtT-D(3) cells. These results indicate that D-264 robustly activates GIRK channels and MAPK coupled to D(2) and D(3) dopamine receptors in AtT-20 cells. D-264 is also a potent inducer of cell proliferation.
authors.affiliation: Department of Pharmacology & Physiology, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Eldo V
authors.initials: EV
authors.lastname: Kuzhikandathil
authors.forename: Samantha
authors.initials: S
authors.lastname: Cote
authors.forename: Soumava
authors.initials: S
authors.lastname: Santra
authors.forename: Aloke K
authors.initials: AK
authors.lastname: Dutta
mesh_terms: D000818:Animals; D052160:Benzothiazoles; D001713:Biphenyl Compounds / Q000494:pharmacology*; D016466:CHO Cells; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D018491:Dopamine Agonists / Q000494:pharmacology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000502:physiology*; D006801:Humans; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D050637:Receptors, Dopamine D3 / Q000819:agonists*; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D052160:Benzothiazoles; D001713:Biphenyl Compounds; D018491:Dopamine Agonists; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C529806:N(6)-(2-(4-(biphenyl-4-yl)piperazin-1-yl)ethyl)-N(6)-propyl-4,5,6,7-tetrahydrobenzo(d)thiazole-2,6-diamine; D010879:Piperazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013844:Thiazoles; D020928:Mitogen-Activated Protein Kinases