Signalling via rat dopamine D2-receptors expressed in mouse fibroblasts is not influenced by compounds binding to the sigma sites of these cells.
The mouse fibroblast cell line LZR-1 is a well-established test system used to characterize the intrinsic activity of dopamine D2-receptor ligands (Neve et al., Mol. Pharmac., 1989). This cell line is transfected with a eucaryotic expression vector containing the gene of the rat dopamine D2B-receptor (short isoform of the D2-receptor) (Bunzow et al., Nature, 1988). In addition to the expression of high levels of the rat dopamine D2-receptor, these mouse cells also express sigma binding sites. Binding affinities of BMY 14,802, DTG, haloperidol, (+)-pentazocine, (+)-3-PPP, and (+)-SKF 10,047 for the sigma binding sites as well as for the D2-dopamine receptor in membranes of LZR-1 cells were determined. Using intact LZR-1 cells, it was found that the influence of sigma ligands on signalling via the dopamine D2-receptor can be explained by their affinity for the latter receptor. Specific sigma ligands did not influence dopaminergic signal transduction in LZR-1 cells. It is therefore concluded that the LZR-1 cell is a suitable test model for determination of the intrinsic activity of dopamine D2-receptor ligands even if these compounds have affinity for sigma binding sites.
Sommermeyer
H
H
Department of Psychopharmacology, Troponwerke GmbH & Co.KG., Köln, F.R.G.
Dompert
W U
WU
Glaser
T
T
D000818:Animals; D001667:Binding, Competitive; D002450:Cell Communication / Q000502:physiology*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism; D006220:Haloperidol / Q000378:metabolism; D051379:Mice; D010423:Pentazocine / Q000378:metabolism; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D017480:Receptors, sigma / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D017448:Receptors, Dopamine D2; D017480:Receptors, sigma; D000242:Cyclic AMP; D006220:Haloperidol; D010423:Pentazocine