Block by apomorphine of acetylcholine receptor channels expressed in Xenopus oocytes.
Effects of apomorphine and other compounds related to dopamine receptors on nicotinic acetylcholine receptor channels were investigated by expressing functional channels in Xenopus oocytes. When channels were expressed with a combination of alpha 3 and beta 4 subunits, acetylcholine activated an inward current, and apomorphine suppressed the current in a concentration-dependent manner with an IC50 value of about 3 microM. SKF38393 (R(+)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol; dopamine D1 receptor agonist; 3 and 30 microM), quinpirole (dopamine D2 receptor agonist; 30 microM), SCH23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benza zepine; dopamine D1 receptor antagonist; 10 microM) or sulpiride (dopamine D2 receptor antagonist; 10 microM) also inhibited the acetylcholine-activated current whereas dopamine (100 microM) was ineffective. The inhibition by apomorphine of the acetylcholine-activated current was also apparent when alpha 3 subunit was combined with beta 2 subunit instead of beta 4 subunit, or beta 4 subunit was combined with alpha 2 or alpha 4 subunit instead of alpha 3 subunit to express channels. The results suggest that apomorphine blocks acetylcholine receptor channels through a binding site that is similar to, but cannot be included in dopamine receptors. The binding site may not be present in a single specific subunit.
Nakazawa
K
K
Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan.
Akiyama
T
T
Inoue
K
K
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001667:Binding, Competitive; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology; D018491:Dopamine Agonists / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000378:metabolism / Q000494:pharmacology; D018733:Nicotinic Antagonists; D009865:Oocytes; D018408:Patch-Clamp Techniques; D019257:Quinpirole; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D013469:Sulpiride / Q000378:metabolism / Q000494:pharmacology; D014158:Transcription, Genetic / Q000235:genetics; D014982:Xenopus laevis
D018491:Dopamine Agonists; D004873:Ergolines; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; D001058:Apomorphine; D004298:Dopamine