THE HUMAN 5-HT1A RECEPTOR - COMPARISON OF ITS BINDING-PROPERTIES IN TRANSFECTED CELLS AND CORTICAL TISSUE

1. The binding characteristics of tritium labeled 8-hydroxy-dipropyl-a minotetralin, or [H-3]8-OH-DPAT, to the serotonin(1A) (5-HT1A) recepto r in the stably transfected HeLa cell clone HA6 and in human cortical tissue were examined and compared. 2. A series of kinetic studies of [ H-3]8-OH-DPAT binding to the transfected HA6 cell line demonstrated tw o components in both the association and the dissociation reactions. 3 . In saturation experiments, at least two affinity states were unequiv ocally detected in the HA6 cell line and the human cortical tissue. Us ing isotopic dilutions, the binding isotherms were best fitted to a tw o-site model, and similar affinity values were obtained in both system s (K-H similar to 1.1 nM and K-L similar to 12-223 nM). 4. Most of the drugs used in competitions inhibited [H-3]8-OH-DPAT binding, followin g a two site model, and maintained their rank order of binding potency in both systems; that is, 5-HT greater than or equal to 8-OH-DPAT> bu spirone> pindolol. Inconsistencies, however, were found for the antago nists NAN-190 and pindolol; only one inhibition constant was determine d for HA6 cells, but two affinities were detected with cortical tissue . 5. The results indicate that, although data from binding studies usi ng the cell expression system reflect, to a certain extent, those obta ined with the cortical tissue, some discrepancies remained. 6. Finally , and in contrast with what is observed with the 5-HT1A receptor expre ssed in the HA6 cell line, it is possible that different receptors, or subtypes of one receptor, or even uptake sites normally expressed in cortical tissue, could interact with [H-3]8-OH-DPAT or the competing d rugs or both, thus leading to the observation of additional binding si tes. (C) 1997 Elsevier Science Inc.