PMID- 7708749
OWN - NLM
STAT- MEDLINE
DCOM- 19950511
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 92
IP  - 7
DP  - 1995 Mar 28
TI  - Effects of serotonergic agents on neuronal nicotinic acetylcholine receptors.
PG  - 2919-23
AB  - In Xenopus oocytes expressing neuronal nicotinic acetylcholine receptors 
      (nAcChoRs), made up of alpha 2 and beta 4 subunits, acetylcholine (AcCho) 
      elicited ionic membrane currents (AcCho currents) that were modulated by 
      serotonergic agents. Both agonists and antagonists specific for various serotonin 
      (5-hydroxytryptamine, 5HT) receptor subtypes interacted directly with alpha 2 
      beta 4 nAcChoRs: 5HT, (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin, methysergide, 
      spiperone, and ketanserin reversibly reduced the amplitude of AcCho currents and 
      accelerated their decay. The AcCho-current time course decayed with two 
      exponential functions. In the presence of 5HT, the fast time constant of current 
      decay (tau f) was not greatly modified, but the slow time constant (tau s) was 
      reduced. With AcCho and 5HT both at 100 microM, tau s was reduced from 140 s to 
      85 s. The order of potency for inhibition of AcCho current amplitudes was 
      (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin > methysergide > spiperone > 
      ketanserin > 5HT. The inhibition was voltage-dependent but the magnitude of the 
      voltage dependence for the different blockers did not correspond to their 
      blocking potency: e.g., the block with spiperone was stronger than with 5HT, but 
      it was less voltage-dependent. Our results suggest that serotonergic agents block 
      neuronal nAcChoRs in a noncompetitive manner, similar to the block of muscle 
      nAcChoR by curare and other substances. These results show that neuronal nAcChoR 
      channels that have been activated by their specific neurotransmitter may be 
      modulated by nonspecific neurotransmitters and their antagonists. These effects 
      may help to better understand brain functions as well as the mode of action of 
      the many serotonergic agents that are used in medical practice.
FAU - Garcia-Colunga, J
AU  - Garcia-Colunga J
AD  - Department of Psychobiology, University of California, Irvine 92717-4550, USA.
FAU - Miledi, R
AU  - Miledi R
LA  - eng
GR  - NS23284/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (Serotonin Antagonists)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 0 (Tetrahydronaphthalenes)
RN  - 333DO1RDJY (Serotonin)
RN  - 4X6E73CJ0Q (Spiperone)
RN  - 97F9DE4CT4 (Ketanserin)
RN  - RR7D75YDF4 (7-hydroxy-2-N,N-dipropylaminotetralin)
RN  - XZA9HY6Z98 (Methysergide)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Electric Conductivity
MH  - Female
MH  - Ketanserin/pharmacology
MH  - Membrane Potentials/drug effects
MH  - Methysergide/pharmacology
MH  - Neurons/*physiology
MH  - Oocytes/drug effects/physiology
MH  - Patch-Clamp Techniques
MH  - Rats
MH  - Receptors, Nicotinic/biosynthesis/*physiology
MH  - Serotonin/*pharmacology
MH  - Serotonin Antagonists/pharmacology
MH  - Serotonin Receptor Agonists/*pharmacology
MH  - Spiperone/pharmacology
MH  - Tetrahydronaphthalenes/pharmacology
MH  - Xenopus laevis
PMC - PMC42330
EDAT- 1995/03/28 00:00
MHDA- 1995/03/28 00:01
PMCR- 1995/09/28
CRDT- 1995/03/28 00:00
PHST- 1995/03/28 00:00 [pubmed]
PHST- 1995/03/28 00:01 [medline]
PHST- 1995/03/28 00:00 [entrez]
PHST- 1995/09/28 00:00 [pmc-release]
AID - 10.1073/pnas.92.7.2919 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2919-23. doi: 10.1073/pnas.92.7.2919.