Blockage of nicotinic acetylcholine receptors by 5-hydroxytryptamine

F. Grassi, L. Polenzani, A. M. Mileo, C. G. Caratsch, F. Eusebi, R. Miledi

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)562-570
Number of pages9
JournalJournal of Neuroscience Research
Volume34
Issue number5
Publication statusPublished - 1993

Fingerprint

Nicotinic Receptors
Serotonin
Oocytes
Skeletal Muscle Fibers
Neurotransmitter Agents
Ligand-Gated Ion Channels
Torpedo
Messenger RNA
Membranes
Xenopus laevis
Xenopus
Baths
Muscles

Keywords

  • 5-hydroxytryptamine
  • C2 myotubes
  • nicotinic acetylcholine receptors
  • TE671/RD medulloblastoma
  • Xenopus oocytes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Grassi, F., Polenzani, L., Mileo, A. M., Caratsch, C. G., Eusebi, F., & Miledi, R. (1993). Blockage of nicotinic acetylcholine receptors by 5-hydroxytryptamine. Journal of Neuroscience Research, 34(5), 562-570.

Blockage of nicotinic acetylcholine receptors by 5-hydroxytryptamine. / Grassi, F.; Polenzani, L.; Mileo, A. M.; Caratsch, C. G.; Eusebi, F.; Miledi, R.

In: Journal of Neuroscience Research, Vol. 34, No. 5, 1993, p. 562-570.

Research output: Contribution to journalArticle

Grassi, F, Polenzani, L, Mileo, AM, Caratsch, CG, Eusebi, F & Miledi, R 1993, 'Blockage of nicotinic acetylcholine receptors by 5-hydroxytryptamine', Journal of Neuroscience Research, vol. 34, no. 5, pp. 562-570.
Grassi F, Polenzani L, Mileo AM, Caratsch CG, Eusebi F, Miledi R. Blockage of nicotinic acetylcholine receptors by 5-hydroxytryptamine. Journal of Neuroscience Research. 1993;34(5):562-570.
Grassi, F. ; Polenzani, L. ; Mileo, A. M. ; Caratsch, C. G. ; Eusebi, F. ; Miledi, R. / Blockage of nicotinic acetylcholine receptors by 5-hydroxytryptamine. In: Journal of Neuroscience Research. 1993 ; Vol. 34, No. 5. pp. 562-570.
@article{c3e24bee2a81412dae43a6d6d3e170b0,
title = "Blockage of nicotinic acetylcholine receptors by 5-hydroxytryptamine",
abstract = "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.",
keywords = "5-hydroxytryptamine, C2 myotubes, nicotinic acetylcholine receptors, TE671/RD medulloblastoma, Xenopus oocytes",
author = "F. Grassi and L. Polenzani and Mileo, {A. M.} and Caratsch, {C. G.} and F. Eusebi and R. Miledi",
year = "1993",
language = "English",
volume = "34",
pages = "562--570",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "5",

}

TY - JOUR

T1 - Blockage of nicotinic acetylcholine receptors by 5-hydroxytryptamine

AU - Grassi, F.

AU - Polenzani, L.

AU - Mileo, A. M.

AU - Caratsch, C. G.

AU - Eusebi, F.

AU - Miledi, R.

PY - 1993

Y1 - 1993

N2 - 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.

AB - 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.

KW - 5-hydroxytryptamine

KW - C2 myotubes

KW - nicotinic acetylcholine receptors

KW - TE671/RD medulloblastoma

KW - Xenopus oocytes

UR - http://www.scopus.com/inward/record.url?scp=0027522313&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027522313&partnerID=8YFLogxK

M3 - Article

C2 - 8478989

AN - SCOPUS:0027522313

VL - 34

SP - 562

EP - 570

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 5

ER -