Block by 5-hydroxytryptamine of neuronal acetylcholine receptor channels expressed in Xenopus oocytes.
1. Effects of 5-hydroxytryptamine (5-HT) on neuronal nicotinic acetylcholine (ACh) receptor channels were investigated by expressing cloned channel subunits in Xenopus oocytes. 2. When channels were expressed with a combination of alpha 3 and beta 4 subunits, 5-HT (10 to 300 microM) reversibly inhibited an inward current activated by 100 microM ACh in a concentration-dependent manner. The inhibition was also observed 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 4-1 subunit instead of alpha 3 subunit to express channels. 3. Compounds known to antagonize at 5-HT receptors (LY53857, metoclopramide and propranolol) exhibited an agonistic effect: they inhibited the ACh-activated current. 4. The results suggest that 5-HT inhibits recombinant neuronal nicotinic receptor channels through a binding-site distinct from conventional 5-HT receptors. The binding-site may not be attributed to a unique type of channel subunits.
Nakazawa
K
K
Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan.
Akiyama
T
T
Inoue
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D018680:Cholinergic Antagonists; D018492:Dopamine Antagonists / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology; D007473:Ion Channels / Q000235:genetics; D008787:Metoclopramide / Q000494:pharmacology; D008845:Microinjections; D009474:Neurons / Q000648:ultrastructure; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D011433:Propranolol / Q000494:pharmacology; D018075:RNA, Complementary / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014981:Xenopus
D000319:Adrenergic beta-Antagonists; D018680:Cholinergic Antagonists; D018492:Dopamine Antagonists; D004873:Ergolines; D007473:Ion Channels; D018733:Nicotinic Antagonists; D018075:RNA, Complementary; D012702:Serotonin Antagonists; D012701:Serotonin; D011433:Propranolol; C032663:LY 53857; D008787:Metoclopramide; D000109:Acetylcholine