Topographical resolution of jaw movements mediated by cyclase- vs. non-cyclase-coupled dopamine D1-like receptors: Studies with SK&F 83822

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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-1H-3-benzazepine), which stimulates dopamine D1-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-1H-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 D2-like agonist quinpirole resulted in synergistic induction of non-chattering movements with tongue protrusions. These effects were blocked by the dopamine D1-like receptor antagonist SCH 23390 ([R]-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine). However, the dopamine D2-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 D1-like receptors participate in synergistic dopamine D1-like:D2-like receptor interactions, topographically specific synergistic and oppositional dopamine D1-like:D2-like interactions evident with SK&F 83822 reflect the involvement primarily of D1-like receptors coupled to AC rather than PI.

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