Topographical resolution of jaw movements mediated by cyclase- vs. non-cyclase-coupled dopamine D 1-like receptors: Studies with SK&F 83822

Abstract

This study examined the effects on orofacial movement topography of SK&F 83822 ([ R/ S]-6-chloro-7,8-dihydroxy-3-allyl-1-[3-methylphenyl]-2,3,4,5-tetrahydro-1 H-3-benzazepine), which stimulates dopamine D 1-like receptors coupled to stimulation of adenylyl cyclase (AC) but not phosphoinositide (PI) hydrolysis, in comparison with SK&F 83959 ([ R/ S]-3-methyl-6-chloro-7,8-dihydroxy-1-[3-methyl-phenyl]-2,3,4,5-tetrahydro-1 H-3-benzazepine), which stimulates PI hydrolysis but not AC. SK&F 83822 alone induced chattering, while SK&F 83959 alone exerted little effect. SK&F 83822 and SK&F 83959 each in combination with the dopamine D 2-like agonist quinpirole resulted in synergistic induction of non-chattering movements with tongue protrusions. These effects were blocked by the dopamine D 1-like receptor antagonist SCH 23390 ([ R]-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine). However, the dopamine D 2-like receptor antagonist YM 09151-2 ( cis- N-[1-benzyl-2-methyl-pyrrolidin-3-yl]-5-chloro-2-methoxy-4-methylaminobenzamide) exerted a biphasic effect on synergism with SK&F 83822: chattering was initially released but antagonised thereafter. Only antagonism was seen for synergism with SK&F 83959. While both AC- and PI-coupled dopamine D 1-like receptors participate in synergistic dopamine D 1-like:D 2-like receptor interactions, topographically specific synergistic and oppositional dopamine D 1-like:D 2-like interactions evident with SK&F 83822 reflect the involvement primarily of D 1-like receptors coupled to AC rather than PI.