Eliahu Heldman

Galila Agam

Liad Mann

Orna Almog

RH Belmaker

Yuly Bersudsky

Annals of General Psychiatry

PubMed

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MEETING ABSTRACT Open Access
Specific inhibition of adenylyl-cyclase isoform
5 by mood stabilizers may be related to their
mechanism of action
Liad Mann, Eliahu Heldman, Yuly Bersudsky, Orna Almog, RH Belmaker, Galila Agam*
From 1st International Congress on Neurobiology and Clinical Psychopharmacology
and European Psychiatric Association Conference on Treatment Guidance
Thessaloniki, Greece. 19-22 November 2009
Lithium, valproate and carbamazepine decrease brain
cAMP. Adenylyl-cyclase (AC), which synthesizes cAMP
has nine membrane-bound isoforms (AC1-AC9). In this
study we used COS7 cells transfected with cDNA of each
of the isoforms to study the effect of a therapeutic concen-
tration of each of lithium, carbamazepine and valproate on
ACs activity. AC5 was the most inhibitable isoform by
lithium and carbamazepine either when stimulated by for-
skolin or by a D1 agonist. Ten mM Mg2+ reduced
lithium-induced AC5 inhibition by 70% and in silico ana-
lysis suggested that carbamazepine preferentially affects
AC1 and AC5 by interacting with two amino-acids at the
catechol-estrogen binding site region. Valproate did not
inhibit any AC isoform suggesting it decreases cAMP
levels via a different mechanism. AC5 knockout mice
behaved in the forced-swim-test similarly to antidepres-
sant- or lithium-treated wildtypes implying that AC5 inhi-
bition may be involved in the antidepressant effect of
lithium and carbamazepine. Specific AC5 inhibitors may
be mood-stabilizers or antidepressants.
Published: 22 April 2010
doi:10.1186/1744-859X-9-S1-S83
Cite this article as: Mann et al.: Specific inhibition of adenylyl-cyclase
isoform 5 by mood stabilizers may be related to their mechanism of
action. Annals of General Psychiatry 2010 9(Suppl 1):S83.
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Psychiatry Research Unit and Department of Clinical Biochemistry, Faculty of
Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
Mann et al. Annals of General Psychiatry 2010, 9(Suppl 1):S83
http://www.annals-general-psychiatry.com/content/9/S1/S83
© 2009 Mann et al.; licensee BioMed Central Ltd.


Specific inhibition of adenylyl-cyclase isoform 5 by mood stabilizers may be related to their mechanism of action

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Specific inhibition of adenylyl-cyclase isoform 5 by mood stabilizers may be related to their mechanism of action

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