IMPORTANCE OF THIOL-GROUPS IN LIGAND-BINDING TO D2-DOPAMINE RECEPTORS FROM BRAIN AND ANTERIOR-PITUITARY GLAND

The effects of the thiol group reagent 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) on D2 dopamine receptors have been examined in three brain regions (caudate nucleus, putamen and olfactory tuberele), and in the anterior and neurointermediate lobes of the pituitary gland. Whereas the receptors in brain were insensitive to DTNB, a dose-dependent inhibition of [H-3]spiperone binding to D2 receptors in both lobes of the pituitary gland was observed. The effects in the pituitary could be reversed by subsequent treatment with dithiothreitol and could be prevented by prior occupancy of the receptor binding site with a ligand. The effect of DTNB was to decrease the number of ligand-binding sites without altering the affinity of those remaining. The results show that modification of a thiol group of the D2 dopamine receptor in the two lobes of the pituitary gland tested here significantly affects ligand binding. There is therefore a difference between the D2 dopamine receptor populations in brain and pituitary in their sensitivity to modification by DTNB, and this may imply the existence of different receptor isoforms in the two issues.