Block by 5-hydroxytryptamine and apomorphine of recombinant human neuronal nicotinic receptors.
The effects of 5-hydroxytryptamine and apomorphine on human neuronal nicotinic acetylcholine receptor/channels were examined by expressing these channels in Xenopus oocytes. Functional channels were expressed by combining one type of alpha subunits (alpha3 or alpha4) and one type of beta subunits (beta2 or beta4). 5-Hydroxytryptamine (100 microM to 1 mM) and apomorphine (10 to 100 microM) inhibited an inward current activated by acetylcholine in the oocytes expressing the channels. The sensitivity to 5-hydroxytryptamine or apomorphine depended on subunit combinations. When concentration-response relationship was obtained for the acetylcholine-activated current, the maximal response was reduced by these compounds. The inhibition by these compounds exhibited voltage-dependence: the inhibition was augmented at negative potentials. The results suggest that 5-hydroxytryptamine and apomorphine noncompetitively inhibits human recombinant nicotinic acetylcholine receptor/channels, presumably by acting on channel pores.
Nakazawa
K
K
Division of Pharmacology, National Institute of Health Sciences, Setagaya, Tokyo, Japan. nakazawa@nihs.go.jp
Ohno
Y
Y
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D009865:Oocytes / Q000502:physiology; D011978:Receptors, Nicotinic / Q000187:drug effects*; D011994:Recombinant Proteins / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D014981:Xenopus / Q000235:genetics
D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D012701:Serotonin; D001058:Apomorphine; D000109:Acetylcholine