Abstract : Nicotinic acetylcholine receptors (nAChRs) are
diverse members of the neurotransmitter-gated ion channel
superfamily and play critical roles in chemical signaling throughout
the nervous system. The present study establishes for the first time
the acute functional effects of sertraline (Zoloft), paroxetine
(Paxil), nefazodone (Serzone), and venlafaxine (Effexor) on two
human and one chick nAChR subtype. This study also confirms previous
findings of nAChR functional block by fluoxetine (Prozac). Function
of human muscle-type nAChR (1) in TE671/RD cells, human autonomic nAChR
(345 ±2) in SH-SY5Y neuroblastoma cells, or chick
V274T mutant 7-nAChR heterologously expressed in native
nAChR-null SH-EP1 epithelial cells was measured using
86Rb+ efflux assays. Functional blockade of
human muscle-type and autonomic nAChRs is produced by each of the
drugs in the low to intermediate micromolar range, and functional
blockade of chick V274T-7-nAChR is produced in the intermediate to
high micromolar range. Functional blockade is insurmountable by
increasing agonist concentrations at each nAChR subtype tested for
each of these drugs, suggesting noncompetitive inhibition of nAChR
function. These studies open the possibilities that nAChR subtypes
in the brain could be targets for therapeutic antidepressants and
could play roles in clinical depression.
Division of Neurobiology, Barrow
Neurological Institute, Phoenix, Arizona, U.S.A.
Abbreviations used : carb, carbamylcholine ; EBDN,
epibatidine ; I-Bgt, 125I-labeled -bungarotoxin ; MLA, methyllycaconitine ;
nAChR, nicotinic acetylcholine receptor ; nicotine, ()-nicotine.
Blackwell Synergy® is a Blackwell Publishing, Inc.
registered trademarkMore information about
Blackwell Synergy - online journals from http://www.blackwellpublishing.com/.We
welcome your Feedback.
See our Privacy
Statement and Terms
and Conditions.Technology Partner - Atypon Systems, Inc.