Blockage of nicotinic acetylcholine receptors by 5-hydroxytryptamine.
The action of 5-hydroxytryptamine (5HT) on nicotinic acetylcholine receptor (nAChR) channels was investigated in mouse myotubes, human cloned TE671/RD cells, and Xenopus laevis oocytes. The decay of the ACh-activated whole-cell currents was reversibly accelerated in the presence of 5HT (10(-5) to 10(-3) M), in a dose-dependent manner. 5HT also reduced the size and accelerated the decay of currents elicited by ACh in Xenopus oocytes injected with mRNA extracted from C2 myotubes or Torpedo electroplaques, or oocytes injected with cloned mouse muscle AChR subunit mRNAs. The effect of 5HT was promptly reversed after washout, or by depolarizing the oocyte beyond -10 mV. In patch-clamp recordings from myotubes, bath-application of 5HT did not exert an indirect influence on the ACh-activated channels within the patch membrane. In contrast, when the patch membrane was exposed to 5HT (10(-6) M), ACh unit responses appeared as bursts of short pulses. It is concluded that the regulation of ACh responses by 5HT results from a fast noncompetitive blocking action of nAChR-channels. These results show that ligand-gated channels, activated by their specific neurotransmitter, may be regulated by a different neurotransmitter through a direct action on the receptor molecule.
Grassi
F
F
Dipartimento Medicina Sperimentale, University of Rome, Italy.
Polenzani
L
L
Mileo
A M
AM
Caratsch
C G
CG
Eusebi
F
F
Miledi
R
R
D000818:Animals; D002460:Cell Line; D002528:Cerebellar Neoplasms / Q000378:metabolism; D018680:Cholinergic Antagonists; D004557:Electric Organ / Q000378:metabolism; D004594:Electrophysiology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D008527:Medulloblastoma / Q000378:metabolism; D051379:Mice; D009132:Muscles / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D011950:Receptors, Cholinergic / Q000096:biosynthesis; D012701:Serotonin / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects; D014101:Torpedo; D014407:Tumor Cells, Cultured; D014981:Xenopus
D018680:Cholinergic Antagonists; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D012701:Serotonin