PT  - JOURNAL ARTICLE
AU  - Logos Curtis
AU  - Bruno Buisson
AU  - Sonia Bertrand
AU  - Daniel Bertrand
TI  - Potentiation of Human α4β2 Neuronal Nicotinic Acetylcholine Receptor by Estradiol
AID  - 10.1124/mol.61.1.127
DP  - 2002 Jan 01
TA  - Molecular Pharmacology
PG  - 127--135
VI  - 61
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/61/1/127.short
4100  - http://molpharm.aspetjournals.org/content/61/1/127.full
SO  - Mol Pharmacol2002 Jan 01; 61
AB  - The modulation of neurotransmitter receptors by various substances can reflect important physiological mechanisms involved in the regulation of neural function. Furthermore, such substances, in particular specific allosteric modulators, can reveal promising therapeutic targets for diseases of the nervous system. From this perspective, we investigated the effects of the steroid hormone estradiol on human neuronal nicotinic acetylcholine receptors expressed either inXenopus laevis oocytes or human embryonic kidney cells. Acetylcholine-evoked currents were potentiated both by pre- and coapplications of estradiol in α4β2 and α4β4 receptors, but not in α3β2 or α3β4 receptors. The reversible potentiation of α4-containing receptors could be induced within seconds in X. laevis oocytes and at micromolar concentrations of estradiol. The potentiation was greatest for responses evoked by low concentrations of acetylcholine, resulting in an apparent increase of receptor affinity. At the single channel level, estradiol potentiation resulted from an increase in opening probability. Finally, the use of functional chimeric or truncated α4 subunits demonstrated that a site at the C-terminal tail of the α4 subunit is required for estradiol potentiation. These results suggest the presence of a specific site at the human nicotinic acetylcholine receptor α4 subunit through which estradiol can cause an allosteric potentiation of acetylcholine-evoked responses.