SK & F 83959 and non-cyclase-coupled dopamine D-1-like receptors in jaw movements via dopamine D-1-like/D-2-like receptor synergism

This study compared the effects of the dopamine D-1-like receptor agents SK &F 83959 (3-methyl-6-chloro-7,8-dihydroxy-1-[3-methylphenyl]-2,3,4,5-tetrah ydro-1 H-3-benzazepine), which inhibits the stimulation of adenylyl cyclase , and A 68930 ([1R,3S]-1-aminomethyl-5,6-dihydroxy-3-phenylisochroman), a f ull efficacy agonist, in regulating jaw movements in the rat by synergism w ith dopamine D-2-Like receptor agonism. When SK&F 83959 and A 68930 were gi ven in combination with quinpirole, there was a synergistic induction of ja w movements. Responsivity to SK&F 83959 + quinpirole was antagonised by the dopamine D-1-like receptor antagonists SCH 23390 ([ R]-3-methyl-7-chloro-8 -hydroxy-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine) and BW 737C ([S]-6- chloro-1-[2,5-dimethoxy-4-propylbenzyl]-7-hydroxy-2-methyl-1,2,3,4-tetrahyd roisoquinoline); synergism was antagonised also by the dopamine D-1-like re ceptor antagonist YM 09151-2 (cis-N-[1-benzyl-2-methyl-pyrrolidin-3-yl]-5-c hloro-2-methoxy-4-methylaminobenzamide). Responsivity to A 68930 + quinpiro le was enhanced by low doses of SCH 23390, BW 737C and YM 09151-2, and anta gonised by higher doses of SCH 23390 and YM 09151-2. These results implicat e a novel, dopamine D-1-like receptor that is coupled to a transduction sys tem other than/additional to adenylyl cyclase, and suggest that its functio nal role extends to the regulation of jaw movements by synergistic interact ions with dopamine D-2-like receptors. (C) 1999 Elsevier Science B.V. All r ights reserved.