G Protein - and -Subunits as Possible Mediators of Dopamine-D1:D2 Receptor Ligand Binding Interactions

Dopamine receptors are members of a large family of neurotransmitter/hormone receptors that exert their biological actions via signal transduction pathways that involve subtype-specific guanine nucleotide binding or G proteins (see Kaziro et al., 1991 ; Simon et al., 1991 ; Hille, 1992 ; Iyengar, 1993 ; Clapham and Neer, 1993 ; Gilman, 1995 ; Rodbell, 1995 ; Raymond, 1995 ). On the basis of biochemical, pharmacological and physiological criteria, receptors for dopamine within the central nervous system and periphery have been classified into two types, termed Dl and D2 (see reviews: Kebabian and Calne, 1979 ; Seeman, 1980 ; Niznik, 1987 ; Niznik and Jarvie 1989 ; Niznik and Van Tol, 1992 ; Kebabian, 1993 ; Hall, 1994 ; Lokhandwala and Chen, 1994 ). Operationally, native membrane-bound dopamine Dl receptors are defined by their ability to stimulate, via G_s or G_olf (Herve et al., 1993 ), adenylate cyclase activity which subsequently activates cAMP-dependent protein kinases (see Hemmings et al., 1987 ; Lovenberg et al., 1991 ; Niznik et al, 1992 ).